大鼠蛛网膜下腔出血后脑微血管的比较蛋白质组分析
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摘要
目的
建立激光捕获显微切割(laser capture microdissection, LCM)技术分离脑微血管和微血管蛋白质组双向凝胶电泳(two-dimensional gelelectrophoresis,2-DE)的技术平台，运用比较蛋白质组学分析鉴定蛛网膜下腔出血(subarachnoid hemorrhage, SAH)后不同时间点脑微血管的差异表达蛋白质，为在蛋白质水平进一步阐明SAH后微血管损伤的分子机制奠定基础。
方法
1建立SAH模型：采用视交叉前池注血法建立大鼠SAH模型。
2分析SAH后脑微血管的动态改变：应用荧光分光光度计和荧光显微镜方法分别检测SAH后不同时间点血脑屏障(blood–brain barrier,BBB)通透性的动态改变，同时利用透射电镜观察其超微结构变化，并确定微血管改变的时相。
3LCM分离SAH后皮质微血管：采用免疫组织化学染色(CD31单克隆抗体)标记微血管内皮细胞，使用LCM分离皮质微血管。
4运用比较蛋白质组学分析SAH后不同时间点脑微血管的差异表达蛋白谱：通过优化2-DE的各种条件和参数，确定最佳的样品上样量、等电聚焦(isoclectfic focusing, IEF)、染色方法等。在此基础上，对SAH后不同时间点脑微血管蛋白质组进行2-DE分离。使用PDQuest软件对2-DE图像进行分析，筛选出不同时间点脑微血管的差异表达蛋白点。候选差异表达蛋白斑点经胶内酶解、基质辅助激光解吸飞行时间质谱(MALDI-TOF-MS)分析，得到肽指纹图谱(peptide mass fingerprint,PMF)，使用Mascot软件在Swiss-Prot或NCBInr数据库中检索鉴定差异表达蛋白质，并对差异蛋白质进行生物信息学分析。
5验证候选差异表达蛋白：使用Western blotting验证感兴趣的蛋白质。
结果
1．SAH后6h时，可见血液广泛分布在前颅窝底、Willis环、基底池周围以及大脑半球和小脑。
2．SAH引起大脑皮质BBB通透性增加。BBB通透性开始增加出现在SAH后24h，于36h达最高峰，然后在48h开始逐渐减少，至72h恢复正常。透射电镜观察，在SAH后36h，毛细血管周围水肿明显，管腔受压；星形胶质细胞足突肿胀，线粒体轻度肿胀，但其细胞膜尚保存；内皮细胞管腔面不光滑，表面微绒毛增多，但紧密连接未见开放；基膜连续且完整。
3．优化PEN切片的固定、染色、脱水等制备方法和LCM切割参数。应用LCM技术分离SAH6h组、SAH36h组皮质微血管，分别得到32000、32500条微血管。
4．通过优化2-DE条件，最终确定合适的样品上样量为120μg、非线性pH3-l0IPG胶条、最佳染色方法为银染。通过对SAH后6h、36h脑微血管蛋白质组的2-DE图像进行对比分析，发现有81个蛋白质斑点表达有差异，其中有48个蛋白点表达明显上调，有33个蛋白点表达明显下调。对其中30个差异蛋白点进行MALDI-TOF-MS和生物信息学分析后，鉴定出了24种可能的差异表达蛋白。
5．Western blotting法对VDAC1、MAPK10两个感兴趣的蛋白质进行了鉴定，结果与2-DE分析的结果一致：与SAH6h组相比，SAH36h组脑微血管中VDAC1、MAPK10蛋白含量均明显增加。
结论
1视交叉前池注血模型更好地模拟临床SAH，重复性好，适合于前循环动脉瘤性SAH后病理生理学机制的研究。
2SAH引起BBB结构和功能最显著的变化出现在36h，而且，这些病理改变对SAH后继发性脑损伤和不良预后有着重要的影响。
3LCM技术是一种强有力的分离方法，能从脑组织中分离出纯度较高的微血管，可用于基因组学和蛋白质组学研究。
4鉴定出的24种差异表达蛋白可能在SAH后脑微血管损伤过程中起重要作用。
Objective
To establish a technical platform of cerebral microvessels isolated bylaser capture microdissection (LCM) and their proteome analyzed bytwo-dimensional gel electrophoresis (2-DE). Further, to investigatedifferentially expressed proteins in cortical microvessels followingsubarachnoid hemorrage in rats by comparative proteomics in order toelucidate the molecular mechanism underlying the microvessel injuryfollowing subarachnoid hemorrage at the protein level.
Methods
1Induction of SAH model in rat: SAH models were induced by aprechiasmatic blood injection technique.
2Analysis of dynamic changes in cortical microvessels after SAH:Blood–brain barrier (BBB) permeability was determined at different timepoints by fluorescence spectrophotometer and fluorescence microscopy,respectively. The ultrastructural changes in BBB were observed withtransmission electron microscope.
3Isolation of cortical microvessels by LCM after SAH: Immunohistochemical staining (antibody to CD31) was employed to labelendothelial cells throughout the cerebral microvascular tree. Selectivemicrodissection of labeled cortical microvessels in frozen tissue sections byLCM.
4Analysis of differentially expressed proteins in cortical microvesselsat different time points following subarachnoid hemorrage in rats bycomparative proteomics: Firstly, optimal parameters and conditions of2-DE were ascertained, including suitable loading quantity of sample, IEF,staining method etc. Secondly, microvessels proteome at various timepoints post-SAH were separated by2-DE. Next, PDQuest software (7.4)was applied to analyze2-DE images to screen differentially expressedprotein spots. Differentially expressed protein spots were subjected todigest with trypsin, and then identified by matrix assisted laserdesorption/isonization time of flying mass spectrometry (MALDI-TOF-MS)to obtain peptide mass fingerprint (PMF). PMF was used to search theSwiss-Prot or NCBInr database with MASCOT search engine.
5Validation of candidate differential proteins: Interesting proteinswere selected and subjected to Western blotting analysis.
Results
1The subarachnoid blood was widely distributed throughout theanterior cranial fossa base, Willis circle, basal cisternal system and over thehemispheres and cerebellum at6h after SAH induction.
2SAH brought about a significant increase in cortical BBBpermeability. BBB permeability began to increase at24hours after SAH,peaked at36hours, and significantly declined at later observations period,normalized at72hours after SAH. Electron micrograph demonstrated at36hours post-SAH, a notable perivascular edema combined with a collapse ofthe capillary. Astrocytic end feet and mitochondria were swollen. Thelumina of the endothelial cells appeared unsmooth. The tight junctions andthe basal laminas were identified normal.
3Preparation methods of PEN tissue sections (including cutting,fixation, immunostaining and dehydration) and microdissection parameterswere optimized before isolation of microvessels by LCM. Approximately32000cortical microvessels from6h group and32500cortical microvesselsfrom36h group were successfully isolated by immuno-LCM.
4Based on optimal conditions and parameters of2-DE, the loadingquantity of sample, category of IPG strips and staining methods weredetermined as120μg, nonlinear IPG strip (pH3-10，17cm) and silverstaining, respectively. Compared with SAH6h group, eighty-onedifferentially expressed protein spots were showed in SAH36h group.Among them, forty-eight protein spots were up-regulated markedly, whilethirty-three protein spots were down-regulated significantly. Thirtydifferential proteins were randomly selected and subjected to identify byMALDI-TOF-MS and bioinformatics analysis. Twenty-four differential proteins were successfully identified.
5To validate the2-DE results, two interesting proteins, VDAC1andMAPK10, were selected and subjected to Western blotting analysis. Theresults showed that both VDAC1and MAPK10had an increasedabundance in SAH36h group as compared with SAH6h group.
Conclusions
1The prechiasmatic blood injection model resembles clinical SAH. Itis very reproducible and appropriate for the study on thepathophysiological mechanisms of aneurysmal SAH in the anteriorcirculation.
2SAH could induce rapid changes in microvascular function andstructure at36hours. Moreover, microvascular dysfunction may play acrucial role in the development of secondary brain injury and unfavorableoutcome.
3LCM technique is a powerful method which could isolate purermicrovessels from complicated brain tissue than other methods, and couldbe applied in the fields of genomics and proteomics.
4Twenty-four differentially expressed proteins identified in this studymight be strongly associated with the development of cerebral microvesselinjury following SAH.
建立激光捕获显微切割(laser capture microdissection, LCM)技术分离脑微血管和微血管蛋白质组双向凝胶电泳(two-dimensional gelelectrophoresis,2-DE)的技术平台，运用比较蛋白质组学分析鉴定蛛网膜下腔出血(subarachnoid hemorrhage, SAH)后不同时间点脑微血管的差异表达蛋白质，为在蛋白质水平进一步阐明SAH后微血管损伤的分子机制奠定基础。
方法
1建立SAH模型：采用视交叉前池注血法建立大鼠SAH模型。
2分析SAH后脑微血管的动态改变：应用荧光分光光度计和荧光显微镜方法分别检测SAH后不同时间点血脑屏障(blood–brain barrier,BBB)通透性的动态改变，同时利用透射电镜观察其超微结构变化，并确定微血管改变的时相。
3LCM分离SAH后皮质微血管：采用免疫组织化学染色(CD31单克隆抗体)标记微血管内皮细胞，使用LCM分离皮质微血管。
4运用比较蛋白质组学分析SAH后不同时间点脑微血管的差异表达蛋白谱：通过优化2-DE的各种条件和参数，确定最佳的样品上样量、等电聚焦(isoclectfic focusing, IEF)、染色方法等。在此基础上，对SAH后不同时间点脑微血管蛋白质组进行2-DE分离。使用PDQuest软件对2-DE图像进行分析，筛选出不同时间点脑微血管的差异表达蛋白点。候选差异表达蛋白斑点经胶内酶解、基质辅助激光解吸飞行时间质谱(MALDI-TOF-MS)分析，得到肽指纹图谱(peptide mass fingerprint,PMF)，使用Mascot软件在Swiss-Prot或NCBInr数据库中检索鉴定差异表达蛋白质，并对差异蛋白质进行生物信息学分析。
5验证候选差异表达蛋白：使用Western blotting验证感兴趣的蛋白质。
结果
1．SAH后6h时，可见血液广泛分布在前颅窝底、Willis环、基底池周围以及大脑半球和小脑。
2．SAH引起大脑皮质BBB通透性增加。BBB通透性开始增加出现在SAH后24h，于36h达最高峰，然后在48h开始逐渐减少，至72h恢复正常。透射电镜观察，在SAH后36h，毛细血管周围水肿明显，管腔受压；星形胶质细胞足突肿胀，线粒体轻度肿胀，但其细胞膜尚保存；内皮细胞管腔面不光滑，表面微绒毛增多，但紧密连接未见开放；基膜连续且完整。
3．优化PEN切片的固定、染色、脱水等制备方法和LCM切割参数。应用LCM技术分离SAH6h组、SAH36h组皮质微血管，分别得到32000、32500条微血管。
4．通过优化2-DE条件，最终确定合适的样品上样量为120μg、非线性pH3-l0IPG胶条、最佳染色方法为银染。通过对SAH后6h、36h脑微血管蛋白质组的2-DE图像进行对比分析，发现有81个蛋白质斑点表达有差异，其中有48个蛋白点表达明显上调，有33个蛋白点表达明显下调。对其中30个差异蛋白点进行MALDI-TOF-MS和生物信息学分析后，鉴定出了24种可能的差异表达蛋白。
5．Western blotting法对VDAC1、MAPK10两个感兴趣的蛋白质进行了鉴定，结果与2-DE分析的结果一致：与SAH6h组相比，SAH36h组脑微血管中VDAC1、MAPK10蛋白含量均明显增加。
结论
1视交叉前池注血模型更好地模拟临床SAH，重复性好，适合于前循环动脉瘤性SAH后病理生理学机制的研究。
2SAH引起BBB结构和功能最显著的变化出现在36h，而且，这些病理改变对SAH后继发性脑损伤和不良预后有着重要的影响。
3LCM技术是一种强有力的分离方法，能从脑组织中分离出纯度较高的微血管，可用于基因组学和蛋白质组学研究。
4鉴定出的24种差异表达蛋白可能在SAH后脑微血管损伤过程中起重要作用。
Objective
To establish a technical platform of cerebral microvessels isolated bylaser capture microdissection (LCM) and their proteome analyzed bytwo-dimensional gel electrophoresis (2-DE). Further, to investigatedifferentially expressed proteins in cortical microvessels followingsubarachnoid hemorrage in rats by comparative proteomics in order toelucidate the molecular mechanism underlying the microvessel injuryfollowing subarachnoid hemorrage at the protein level.
Methods
1Induction of SAH model in rat: SAH models were induced by aprechiasmatic blood injection technique.
2Analysis of dynamic changes in cortical microvessels after SAH:Blood–brain barrier (BBB) permeability was determined at different timepoints by fluorescence spectrophotometer and fluorescence microscopy,respectively. The ultrastructural changes in BBB were observed withtransmission electron microscope.
3Isolation of cortical microvessels by LCM after SAH: Immunohistochemical staining (antibody to CD31) was employed to labelendothelial cells throughout the cerebral microvascular tree. Selectivemicrodissection of labeled cortical microvessels in frozen tissue sections byLCM.
4Analysis of differentially expressed proteins in cortical microvesselsat different time points following subarachnoid hemorrage in rats bycomparative proteomics: Firstly, optimal parameters and conditions of2-DE were ascertained, including suitable loading quantity of sample, IEF,staining method etc. Secondly, microvessels proteome at various timepoints post-SAH were separated by2-DE. Next, PDQuest software (7.4)was applied to analyze2-DE images to screen differentially expressedprotein spots. Differentially expressed protein spots were subjected todigest with trypsin, and then identified by matrix assisted laserdesorption/isonization time of flying mass spectrometry (MALDI-TOF-MS)to obtain peptide mass fingerprint (PMF). PMF was used to search theSwiss-Prot or NCBInr database with MASCOT search engine.
5Validation of candidate differential proteins: Interesting proteinswere selected and subjected to Western blotting analysis.
Results
1The subarachnoid blood was widely distributed throughout theanterior cranial fossa base, Willis circle, basal cisternal system and over thehemispheres and cerebellum at6h after SAH induction.
2SAH brought about a significant increase in cortical BBBpermeability. BBB permeability began to increase at24hours after SAH,peaked at36hours, and significantly declined at later observations period,normalized at72hours after SAH. Electron micrograph demonstrated at36hours post-SAH, a notable perivascular edema combined with a collapse ofthe capillary. Astrocytic end feet and mitochondria were swollen. Thelumina of the endothelial cells appeared unsmooth. The tight junctions andthe basal laminas were identified normal.
3Preparation methods of PEN tissue sections (including cutting,fixation, immunostaining and dehydration) and microdissection parameterswere optimized before isolation of microvessels by LCM. Approximately32000cortical microvessels from6h group and32500cortical microvesselsfrom36h group were successfully isolated by immuno-LCM.
4Based on optimal conditions and parameters of2-DE, the loadingquantity of sample, category of IPG strips and staining methods weredetermined as120μg, nonlinear IPG strip (pH3-10，17cm) and silverstaining, respectively. Compared with SAH6h group, eighty-onedifferentially expressed protein spots were showed in SAH36h group.Among them, forty-eight protein spots were up-regulated markedly, whilethirty-three protein spots were down-regulated significantly. Thirtydifferential proteins were randomly selected and subjected to identify byMALDI-TOF-MS and bioinformatics analysis. Twenty-four differential proteins were successfully identified.
5To validate the2-DE results, two interesting proteins, VDAC1andMAPK10, were selected and subjected to Western blotting analysis. Theresults showed that both VDAC1and MAPK10had an increasedabundance in SAH36h group as compared with SAH6h group.
Conclusions
1The prechiasmatic blood injection model resembles clinical SAH. Itis very reproducible and appropriate for the study on thepathophysiological mechanisms of aneurysmal SAH in the anteriorcirculation.
2SAH could induce rapid changes in microvascular function andstructure at36hours. Moreover, microvascular dysfunction may play acrucial role in the development of secondary brain injury and unfavorableoutcome.
3LCM technique is a powerful method which could isolate purermicrovessels from complicated brain tissue than other methods, and couldbe applied in the fields of genomics and proteomics.
4Twenty-four differentially expressed proteins identified in this studymight be strongly associated with the development of cerebral microvesselinjury following SAH.
引文
[1] van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid hemorrhage [J]. Lancet.2007,369(9558):306-318.
[2] Hansen-Schwartz J, Vajkoczy P, Macdonald RL, et al. Cerebral vasospasm: lookingbeyond vasoconstriction [J]. Trends Pharmacol Sci.2007,28(6):252-256.
[3] Sehba FA, Bederson JB. Mechanisms of acute brain injury after subarachnoidhemorrhage [J]. Neurol Res.2006,28(4):381-398.
[4] Prunell GF, Mathiesen T, Svendgaard NA. A new experimental model in rats forstudy of the pathophysiology of subarachnoid hemorrhage [J]. Neuroreport.2002,13(18):2553-2556.
[5] Schwartz AY, Masago A, Sehba FA, et al. Experimental models of subarachnoidhemorrhage in the rat: a refinement of the endovascular filament model [J]. JNeurosci Methods.2000,96(2):161-167.
[6] Bederson JB，Germano IM，Guarino L．Cortical blood flow and cerebral perfusionpressure in a new noncraniotomy model of subarachnoid hemorhage in the rat [J].Stroke, l995,26(6): l086-1092.
[7] Megyesi JF, Vollrath B, Cook DA, et al. In vivo animal models of cerebralvasospasm: A review [J]. Neurosurgery.2000,46(2):448-461.
[8] Velthuis BK, Rinkel GJ, Ramos LM, et al. Subarachnoid hemorrhage: aneurysmdetection and preoperative evaluation with CT angiography [J]. Radiology.1998,208(2):423-430.
[9] Xi G, Hua Y, Keep RF, et al. Brain edema after intracerebral hemorrhage: the effectsof systemic complement depletion [J]. Acta Neurochir Suppl.2002,81:253–256.
[10]Uyama O, Okamura N, Yanase M, et al. Quantitative evaluation of vascularpermeability in the gerbil brain after transient ischemia using Evans bluefluorescence [J]. J Cereb Blood Flow Metab.1988,8(2):282-284.
[11]Bertram KJ, Shipley MT, Ennis M, et al. Permeability of the blood-brain barrierwithin rat intrastriatal transplants assessed by simultaneous systemic injection ofhorseradish peroxidase and Evans blue dye [J]. Exp Neurol.1994,127(2):245-252.
[12]Saria A, Lundberg JM. Evans blue fluorescence: Quantitative and morphologicalevaluation of vascular permeability in animal tissues [J]. J Neurosci Methods.1983,8(1):81-89.
[13]Belayev L, Brsto R, Zhao W, et al. Quantitative evaluation of blood-brain barrierpermeability following middle cerebral artery occlusion in rats [J]. Brain Res.1996,739(1):88-96.
[14]邝芳,王百忍,王凌,等.利用伊文思蓝的荧光显示肾上腺素诱发的血脑屏障开放[J].神经解剖学杂志.1997,13(4):417-420.
[15]Carrera RM, Pacheco AM Jr, Mastroti RA. Qualitative evaluation of theblood-brain barrier after the use of hypertonic saline solution in young rats [J]. EurSurg Res.2001,33(5-6):311-317.
[16]Germano A, d’Avella D, Imperatore C, et al. Time-course of blood brain barrierpermeability changes after experimental subarachnoid hemorrhage [J]. ActaNeurochir (Wien).2000,142(5):575-581.
[17]Fischer S, Wobben M, Marti HH, et al. Hypoxia-induced hyperpermeability in brainmicrovessel endothelial cells involves VEGF-mediated changes in the expression ofzonula occludens-1[J]. Microvasc Res.2002,63(1):70-80.
[18]Krizbai IA, Deli MA. Signalling pathways regulating the tight junctionpermeability in the blood-brain barrier [J]. Cell Mol Biol (Noisy-le-grand).2003,49(1):23-31.
[19]Abbott NJ. Astrocyte-endothelial interactions and blood-brain barrier permeability[J]. J Anat.2002,200(6):629-38.
[20]Li YQ, Chen P, Haimovitz-Friedman A, et al. Endothelial apoptosis initiates acuteblood-brain barrier disruption after ionizing radiation [J]. Cancer Res.2003,63(18):5950-5956.
[21]Stewart PA. Endothelial vesicles in the blood-brain barrier: are they related topermeability?[J]. Cell Mol Neurobiol.2000,20(2):149-163.
[22]Doczi T. The pathogenetic and prognostic significance of blood-brain barrierdamage at the acute stage of aneurismal subarachnoid haemorrhage. Clinical andexperimental studies [J]. Acta Neurochir (Wien).1985,77(3-4):110-132.
[23]Trojanowski T. Blood-brain barrier changes after experimental subarachnoidhaemorrhage [J]. Acta Neurochir (Wien).1982,60(1-2):45-54.
[24]Doczi T, Joo F, Adam G, et al. Blood-brain barrier damage during the acute stage ofsubarachnoid hemorrhage, as exemplified by a new animal model [J]. Neurosurgery.1986,18(6):733-739.
[25]Jacowski A, Crockard A, Burnstock G, et al. The time course of intracranialpathophysiological changes following experimental subarachnoid haemorrhage inthe rat [J]. J Cereb Blood Flow Metab.1990,10(6):835–849.
[26]d’Avella D, Cicciarello R, Zuccarello M, et al. Brain energy metabolism in theacute stage of experimental subarachnoid haemorrhage: local changes in cerebralglucose utilization [J]. Acta Neurochir (Wien).1996,138(6):737–744.
[27]Imperatore C, Germano A, d'Avella D, et al. Effects of the radical scavanger AVSon behavioral and BBB changes after experimental subarachnoid haemorrhage [J].Life Sciences.2000,66(9):779-790.
[28]Sehba FA, Mostafa G, Knopman J, et al. Acute alterations in microvascular basallamina after subarachnoid hemorrhage [J]. J Neurosurg.2004,101(4):633–640.
[29]Mayhan WG. VEGF increases permeability of the blood-brain barrier via a nitricoxide synthase/cGMP-dependent pathway [J]. Am J Physiol.1999,276(5):C1148–C53.
[30]Kusaka G, Ishikawa M, Nanda A, et al. Signaling pathways for early brain injuryafter subarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2004,24(8):916–25.
[31]Sercombe R, Dinh YR, Gomis P. Cerebrovascular inflammation followingsubarachnoid hemorrhage [J]. Jpn J Pharmacol.2002,88(3):227–249
[32]Yatsushige H, Ostrowski RP, Tsubokawa T, et al. Role of c-Jun N-terminal kinase inearly brain injury after subarachnoid hemorrhage [J]. J Neurosci Res.2007,85(7):1436-1448.
[33]Cahill J, Calvert JW, Marcantonio S, et al. p53may play an orchestrating role inapoptotic cell death after experimental subarachnoid hemorrhage [J]. Neurosurgery.2007,60(3):531-545.
[34]Park S, Yamaguchi M, Zhou C, et al. Neurovascular protection reduces early braininjury after subarachnoid hemorrhage [J]. Stroke.2004,35(10):2412–2417.
[35]Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injuryafter subarachnoid hemorrhage [J]. Neurol Res.2006,28(4):399–414.
[36]Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury aftersubarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2006,26(11):1341-1353.
[37]Claassen J, Carhuapoma JR, Kreiter KT, et al. Global cerebral edema aftersubarachnoid hemorrhage: frequency, predictors, and impact on outcome [J]. Stroke.2002,33(5):1225-1232.
[38]Mocco J, Prickett CS, Komotar RJ, et al. Potential mechanisms and clinicalsignificance of global cerebral edema following aneurysmal subarachnoidhemorrhage [J]. Neurosurg Focus.2007,22(5): E7.
[39]Germanò A, Caffo M, Angileri FF et al. NMDA receptor antagonist felbamatereduces behavioral deficits and blood-brain barrier permeability changes afterexperimental subarachnoid hemorrhage in the rat [J]. J Neurotrauma.2007,24(4):732-744.
[1] Abbort A. And now for the proteome [J]. Nature.2001,409(6822):747.
[2] Tyers M, Mann M. From genomics to proteomics [J]. Nature.2003,422(6928):193-197.
[3] Sali A, Glaeser R, Earnest T, et al. From words to literature in structural proteomics[J]. Nature.2003,422(6928):216-225.
[4] Aittokallio T, Salmi J, Nyman TA, et al. Geometrical distortions in two-dimensionalgels: applicable correction methods [J]. J Chromatogr B Analyt Technol BiomedLife Sci.2005,815(1-2):25-37.
[5] The Protocol Guide for Leica Laser Microdissection Systems.http://www.leica-microsystems.com.
[6] Boado RJ, Pardridge WM. A one-step procedure for isolation of poly(A)+mRNAfrom isolated brain capillaries and endothelial cells in culture [J]. J Neurochem.1991,57(6):2136–2139.
[7] Yousif S, Marie-Claire C, Roux F, et al. Expression of drug transporters at theblood-brain barrier using an optimized isolated rat brain microvessel strategy [J].Brain Res.2007,1134(1):1-11.
[8] Calabria AR, Shusta EV. Blood-brain barrier genomics and proteomics: elucidatingphenotype, identifying disease targets and enabling brain drug delivery [J]. DrugDiscov Today.2006,11(17-18):792-799.
[9] Emmert-Buck MR, Bonner RF, Smith PD, et al. Laser capture microdissection [J].Science.1996,274(5289):998-1001.
[10]Espina V, Milia J, Wu G, et al. Laser capture microdissection [J]. Methods Mol Biol.2006,319:213-229.
[11]Simone NL, Bonner RF, Gillespie JW, et al. Laser-capture microdissection:opening the microscopic frontier to molecular analysis [J]. Trends Genet.1998,14(7):272-276.
[12]Espina V, Heiby M, Pierobon M, et al. Laser capture microdissection technology[J]. Expert Rev Mol Diagn.2007,7(5):647-657.
[13]Xu C, Houck JR, Fan W, et al. Simultaneous Isolation of DNA and RNA from theSame Cell Population Obtained by Laser Capture Microdissection for Genome andTranscriptome Profiling [J]. J Mol Diagn.2008,10(2):129-134.
[14]Espina V, Wulfkuhle JD, Calvert VS, et al. Laser-capture microdissection [J]. NatProtoc.2006,1(2):586-603.
[15]von Eggeling F, Melle C, Ernst G. Microdissecting the proteome [J]. Proteomics.2007,7(16):2729-2737.
[16] Ball HJ, McParland B, Driussi C, et al. Isolating vessels from the mouse brain forgene expression analysis using laser capture microdissection [J]. Brain Res BrainRes Protoc.2002,9(3):206-213.
[17]Craven RA, Totty N, Harnden P, et al. Laser capture microdissection andtwo-dimensional polyacrylamide gel electrophoresis: evaluation of tissuepreparation and sample limitations [J]. Am J Pathol.2002,160(3):815-822.
[18]Fend F, Emmert-Buck MR, Chuaqui R, et al. Immuno-LCM: laser capturemicrodissection of immunostained frozen sections for mRNA analysis [J]. Am JPathol.1999,154(1):61-66.
[19]Moulédous L, Hunt S, Harcourt R, et al. Proteomic analysis of immunostained,laser-capture microdissected brain samples [J]. Electrophoresis.2003,24(1-2):296-302.
[20]De Souza AI, McGregor E, Dunn MJ, et al. Preparation of human heart for lasermicrodissection and proteomics [J]. Proteomics.2004,4(3):578-586.
[21]Leverenz JB, Umar I, Wang Q, et al. Proteomic identification of novel proteins incortical lewy bodies [J]. Brain Pathol.2007,17(2):139-145.
[22]Moulédous L, Hunt S, Harcourt R, et al. Navigated laser capture microdissection asan alternative to direct histological staining for proteomic analysis of brain samples[J]. Proteomics.2003,3(5):610-615.
[23]Gutstein HB, Morris JS. Laser capture sampling and analytical issues in proteomics[J]. Expert Rev Proteomics.2007,4(5):627-637.
[24]陈主初,梁宋平等.肿瘤蛋白质组学[M].湖南科学技术出版社.2002,23-24.
[25]G rg A, Weiss W, Dunn MJ. Current two-dimensional electrophoresis technologyfor proteomics [J]. Proteomics.2004,4(12):3665-3685.
[26]G rg A, Obermaier C, Boguth G, et al. The current state of two-dimensionalelectrophoresis with immobilized pH gradients [J]. Electrophoresis.2000,21(6):1037-1053.
[27]Herbert BR, Molloy MP, Gooley AA, et al. Improved protein solubility intwo-dimensional electrophoresis using tributyl phosphine as reducing agent [J].Electrophoresis.1998,19(5):845-851.
[28]夏其昌,曾嵘等.蛋白质化学与蛋白质组学[M].科学出版社.2004,271-274.
[29]Celis JE, Carter N, Hunter T, et al. Protein detection in gels by silver staining：aprocedure compatible with mass-spectrometry. Cell Biology: a laboratoryhandbook(3rd Edition)[M]. Elsevier. Academic Press.2006.219-223.
[1] van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage [J]. Lancet.2007,369(9558):306-318.
[2] Kozniewska E, Michalik R, Rafalowska J, et al. Mechanisms of vasculardysfunction after subarachnoid hemorrhage [J]. J Physiol Pharmacol.2006,57(suppl11):145-160.
[3] Sehba FA, Bederson JB. Mechanisms of acute brain injury after subarachnoidhemorrhage [J]. Neurol Res.2006,28(4):381-98.
[4] Claassen J, Carhuapoma JR, Kreiter KT, et al. Global cerebral edema aftersubarachnoid hemorrhage: frequency, predictors, and impact on outcome [J]. Stroke.2002,33(5):1225-1232.
[5] Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injuryafter subarachnoid hemorrhage [J]. Neurol Res.2006,28(4):399-414.
[6] Mocco J, Prickett CS, Komotar RJ, et al. Potential mechanisms and clinicalsignificance of global cerebral edema following aneurysmal subarachnoidhemorrhage [J]. Neurosurg Focus.2007,22(5): E7.
[7] Ohkuma H, Manabe H, Tanaka M, et al. Impact of cerebral microcirculatorychanges on cerebral blood flow during cerebral vasospasm after aneurysmalsubarachnoid hemorrhage [J]. Stroke.2000,31(7):1621-1627.
[8] Tyers M, Mann M. From genomics to proteomics [J]. Nature.2003,422(6928):193-197.
[9] Paulson L, Martin P, Persson A, et al. Comparative genome-and proteome analysisof cerebral cortex from MK-801-treated rats [J]. J Neurosci Res.2003,71(4):526-533.
[10]Shevchenko A, Tomas H, Havlis J, et al. In-gel digestion for mass spectrometriccharacterization of proteins and proteomes [J]. Nat Protoc.2006,1(6):2856-2860.
[11]Macdonald RL, Pluta RM, Zhang JH. Cerebral vasospasm after subarachnoidhemorrhage: the emerging revolution [J]. Nat Clin Pract Neurol.2007,3(5):256-263.
[12]Treggiari-Venzi MM, Suter PM, Romand JA. Review of medical prevention ofvasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensivecare [J]. Neurosurgery.2001,48(2):249-262.
[13]Rabinstein AA, Friedman JA, Weigand SD, et al. Predictors of cerebral infarction inaneurysmal subarachnoid hemorrhage [J]. Stroke.2004,35(8):1862–1866.
[14]Rabinstein AA, Weigand S, Atkinson JL, et al. Patterns of cerebral infarction inaneurysmal subarachnoid hemorrhage [J]. Stroke.2005,36(5):992–997.
[15]Del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia [J]. JCereb Blood Flow Metab.2003,23(8):879-894.
[16][16] Uhl E, Lehmberg J, Steiger HJ, et al. Intraoperative detection of earlymicrovasospasm in patients with subarachnoid hemorrhage by using orthogonalpolarization spectral imaging [J]. Neurosurgery.2003,52(6):1307-1317.
[17]Pennings FA, Bouma GJ, Ince C. Direct observation of the human cerebralmicrocirculation during aneurysm surgery reveals increased arteriolar contractility[J]. Stroke.2004,35(6):1284-1288.
[18]Yamamoto S, Nishizawa S, Tsukada H, et al. Cerebral autoregulation followingsubarachnoid hemorrhage in rats: chronic vasospasm shifts the upper and lowerlimits of the autoregulatory range toward higher blood pressure [J]. Brain Res.1998,782(1-2):194-201.
[19]Weidauer S, Vatter H, Beck J, et al. Focal laminar cortical infarcts followinganeurysmal subarachnoid haemorrhage [J]. Neuroradiology.2008,50(1):1-8.
[20]Sehba FA, Mostafa G, Friedrich V, et al. Acute microvascular platelet aggregationafter subarachnoid hemorrhage [J]. J Neurosurg.2005,102(6):1094–1100.
[21]Sehba FA, Mostafa G, Knopman J, et al. Acute alterations in microvascular basallamina after subarachnoid hemorrhage [J]. J Neurosurg.2004,101(4):633-40.
[22]Sehba FA, Friedrich V Jr, Makonnen G, et al. Acute cerebral vascular injury aftersubarachnoid hemorrhage and its prevention by administration of a nitric oxidedonor [J]. J Neurosurg.2007,106(2):321-329.
[23]Sch ller K, Trinkl A, Klopotowski M, et al. Characterization of microvascularbasal lamina damage and blood-brain barrier dysfunction following subarachnoidhemorrhage in rats [J]. Brain Res.2007,1142:237-246.
[24]Lassalle P, Molet S, Janin A, et al. ESM-1is a novel human endothelial cell-specificmolecule expressed in lung and regulated by cytokines [J]. J Biol Chem.1996,271(34):20458-20464.
[25]Bechard D, Meignin V, Scherpereel A, et al. Characterization of the secreted formof endothelial-cell-specific molecule1by specific monoclonal antibodies [J]. J VascRes.2000,37(5):417-425.
[26]Sarrazin S, Adam E, Lyon M, et al. Endocan or endothelial cell specific molecule-1(ESM-1): a potential novel endothelial cell marker and a new target for cancertherapy [J]. Biochim Biophys Acta.2006,1765(1):25-37.
[27]van Gurp M, Festjens N, van Loo G, et al. Mitochondrial intermembrane proteins incell death [J]. Biochem Biophys Res Commun.2003,304(3):487-497.
[28]Jensen RE, Dunn CD. Protein import into and across the mitochondrial innermembrane: role of the TIM23and TIM22translocons [J]. Biochim Biophys Acta.2002,1592(1):25-34.
[29]Kutik S, Guiard B, Meyer HE, et al. Cooperation of translocase complexes inmitochondrial protein import [J]. J Cell Biol.2007,179(4):585-591.
[30]Morimoto RI. Cells in stress: transcriptional activation of heat shock genes [J].Science.1993,259(5100):1409-1410.
[31]Haslbeck M. sHsps and their role in the chaperone network [J]. Cell Mol Life Sci.2002,59(10):1649-1657.
[32]David JC, Boelens WC, Grongnet JF. Up-regulation of heat shock protein HSP20in the hippocampus as an early response to hypoxia of the newborn [J]. JNeurochem.2006,99(2):570-581.
[33]Smith SL, Scherch HM, Hall ED. Protective effects of tirilazad mesylate andmetabolite U-89678against blood-brain barrier damage after subarachnoidhemorrhage and lipid peroxidative neuronal injury [J]. J Neurosurg.1996,84(2):229-233.
[34]Sen O, Caner H, Aydin MV, et al. The effect of mexiletine on the level of lipidperoxidation and apoptosis of endothelium following experimental subarachnoidhemorrhage [J]. Neurol Res.2006,28(8):859-863.
[35]Ostrowski RP, Tang J, Zhang JH. Hyperbaric oxygen suppresses NADPH oxidasein a rat subarachnoid hemorrhage model [J]. Stroke.2006,37(5):1314-1318.
[36]Nilius B, Droogmans G. Amazing chloride channels: an overview [J]. Acta PhysiolScand.2003,177(2):119-147.
[37]Suh KS, Mutoh M, Nagashima K, et al. The organellular chloride channel proteinCLIC4/mtCLIC translocates to the nucleus in response to cellular stress andaccelerates apoptosis [J]. J Biol Chem.2004,279(6):4632-4641.
[38]Suh KS, Mutoh M, Gerdes M, et al. CLIC4, an intracellular chloride channelprotein, is a novel molecular target for cancer therapy [J]. J Investig DermatolSymp Proc.2005,10(2):105-109.
[39]Suginta W, Karoulias N, Aitken A, et al. Chloride intracellular channel proteinCLIC4(p64H1) binds directly to brain dynamin I in a complex containing actin,tubulin and14-3-3isoforms [J]. Biochem J.2001,359(Pt1):55-64.
[40]Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury aftersubarachnoid hemorrhage [J]. J Cereb Blood Flow Metab,2006,26(11):1341-1353.
[41]Zhou C, Yamaguchi M, Kusaka G, et al. Caspase inhibitors prevent endothelialapoptosis and cerebral vasospasm in dog model of experimental subarachnoidhemorrhage [J]. J Cereb Blood Flow Metab.2004,24(4):419–431.
[42]Park S, Yamaguchi M, Zhou C, et al. Neurovascular protection reduces early braininjury after subarachnoid hemorrhage [J]. Stroke.2004,35(10):2412–2417.
[43]Hawkins TE, Merrifield CJ, Moss SE. Calcium signaling and annexins [J]. CellBiochem Biophys.2000,33(3):275-296.
[44]Gerke V, Moss SE. Annexins: from structure to function [J]. Physiol Rev.2002,82(2):331-371.
[45]Hayes MJ, Moss SE. Annexins and disease [J]. Biochem Biophys Res Commun.2004,322(4):1166-1170.
[46]Reutelingsperger CP. Annexins: key regulators of haemostasis, thrombosis, andapoptosis [J]. Thromb Haemost.2001,86(1):413-419.
[47]Boersma HH, Kietselaer BL, Stolk LM, et al. Past, present, and future of annexinA5: from protein discovery to clinical applications [J]. J Nucl Med.2005,46(12):2035-2050.
[48]Kenis H, Hofstra L, Reutelingsperger CP. Annexin A5: shifting from a diagnostictowards a therapeutic realm [J]. Cell Mol Life Sci.2007,64(22):2859-2862.
[49]Nicholl SM, Roztocil E, Davies MG. Plasminogen activator system and vasculardisease [J]. Curr Vasc Pharmacol.2006,4(2):101-116.
[50]Lindgren A, Lindoff C, Norrving B, et al. Tissue plasminogen activator andplasminogen activator inhibitor-1in stroke patients [J]. Stroke.1996,27(6):1066-1071.
[51]Peltonen S, Juvela S, Kaste M, et al. Hemostasis and fibrinolysis activation aftersubarachnoid hemorrhage [J]. J Neurosurg.1997,87(2):207-214.
[52]Vergouwen MD, Frijns CJ, Roos YB, et al. Plasminogen activator inhibitor-14Gallele in the4G/5G promoter polymorphism increases the occurrence of cerebralischemia after aneurysmal subarachnoid hemorrhage [J]. Stroke.2004,35(6):1280-1283.
[53]Roos YB, Levi M, Carroll TA, et al. Nimodipine increases fibrinolytic activity inpatients with aneurysmal subarachnoid hemorrhage [J]. Stroke.2001,32(8):1860-1862.
[54]Blalock JE. A molecular basis for bidirectional communication between theimmune and neuroendocrine systems [J]. Physiol Rev.1989,69(1):1-32.
[55]Basu A, Krady JK, Levison SW. Interleukin-1: a master regulator ofneuroinflammation [J]. J Neurosci Res.2004,78(2):151-156.
[56]Pinteaux E, Rothwell NJ, Boutin H. Neuroprotective actions of endogenousinterleukin-1receptor antagonist (IL-1ra) are mediated by glia [J]. Glia.2006,53(5):551-556.
[57]Towne JE, Garka KE, Renshaw BR, et al. Interleukin (IL)-1F6, IL-1F8, and IL-1F9signal through IL-1Rrp2and IL-1RAcP to activate the pathway leading toNF-kappaB and MAPKs [J]. J Biol Chem.2004,279(14):13677-13688.
[58]Li X, Stark GR. NFkappaB-dependent signaling pathways [J]. Exp Hematol.2002,30(4):285-296.
[59]Gallia GL, Tamargo RJ. Leukocyte-endothelial cell interactions in chronicvasospasm after subarachnoid hemorrhage [J]. Neurol Res.2006,28(7):750-758.
[60]Abbott NJ. Inflammatory mediators and modulation of blood-brain barrierpermeability [J]. Cell Mol Neurobiol.2000,20(2):131-147.
[61]Fassbender K, Hodapp B, Rossol S, et al. Inflammatory cytokines in subarachnoidhaemorrhage: association with abnormal blood flow velocities in basal cerebralarteries [J]. J Neurol Neurosurg Psychiatry.2001,70(4):534-537.
[62]Sercombe R, Dinh YR, Gomis P. Cerebrovascular inflammation followingsubarachnoid hemorrhage [J]. Jpn J Pharmacol.2002,88(3):227-249.
[63]Dean DC, Iademarco MF, Rosen GD, et al. The integrin alpha4beta1and itscounter receptor VCAM-1in development and immune function [J]. Am RevRespir Dis.1993,148(6Pt2): S43-46.
[64]Newman PJ, Berndt MC, Gorski J, et al. PECAM-1(CD31) cloning and relation toadhesion molecules of the immunoglobulin gene superfamily [J]. Science.1990,247(4947):1219-1222.
[65]Woodfin A, Voisin MB, Nourshargh S. PECAM-1: a multi-functional molecule ininflammation and vascular biology [J]. Arterioscler Thromb Vasc Biol.2007,27(12):2514-2523.
[66]Kaynar MY, Tanriverdi T, Kafadar AM, et al. Detection of soluble intercellularadhesion molecule-1and vascular cell adhesion molecule-1in both cerebrospinalfluid and serum of patients after aneurysmal subarachnoid hemorrhage [J]. JNeurosurg.2004,101(6):1030-1036.
[67]Rothoerl RD, Schebesch KM, Kubitza M, et al. ICAM-1and VCAM-1expressionfollowing aneurysmal subarachnoid hemorrhage and their possible role in thepathophysiology of subsequent ischemic deficits [J]. Cerebrovasc Dis.2006,22(2-3):143-149.
[68]Rothoerl RD, Ringel F. Molecular mechanisms of cerebral vasospasm followinganeurysmal SAH [J]. Neurol Res.2007,29(7):636-642.
[69]Nissen JJ, Mantle D, Gregson B, et al. Serum concentration of adhesion moleculesin patients with delayed ischaemic neurological deficit after aneurysmalsubarachnoid haemorrhage: the immunoglobulin and selectin superfamilies [J]. JNeurol Neurosurg Psychiatry.2001,71(3):329-333.
[70]Yancopoulos GD, Klagsbrun M, Folkman J. Vasculogenesis, angiogenesis, andgrowth factors: ephrins enter the fray at the border [J]. Cell.1998,93(5):661-664.
[71]Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, andgrowth in tumors mediated by angiopoietins and VEGF [J]. Science.1999,284(5422):1994-1998.
[72]Yancopoulos GD, Davis S, Gale NW, et al. Vascular-specific growth factors andblood vessel formation [J]. Nature.2000,407(6801):242-248.
[73]Lin TN, Wang CK, Cheung WM, et al. Induction of angiopoietin and Tie receptormRNA expression after cerebral ischemia-reperfusion [J]. J Cereb Blood FlowMetab.2000,20(2):387-395.
[74]Zhang Z, Chopp M. Vascular endothelial growth factor and angiopoietins in focalcerebral ischemia [J]. Trends Cardiovasc Med.2002,12(2):62-66.
[75]Zhang ZG, Zhang L, Tsang W, et al. Correlation of VEGF and angiopoietinexpression with disruption of blood-brain barrier and angiogenesis after focalcerebral ischemia [J]. J Cereb Blood Flow Metab.2002,22(4):379-392.
[76]Zhu Y, Lee C, Shen F, et al. Angiopoietin-2facilitates vascular endothelial growthfactor-induced angiogenesis in the mature mouse brain [J]. Stroke.2005,36(7):1533-1537.
[77]Nag S, Papneja T, Venugopalan R, et al. Increased angiopoietin2expression isassociated with endothelial apoptosis and blood-brain barrier breakdown [J]. LabInvest.2005,85(10):1189-1198.
[78]Zhang ZG, Zhang L, Croll SD, Chopp M. Angiopoietin-1reduces cerebral bloodvessel leakage and ischemic lesion volume after focal cerebral embolic ischemia inmice [J]. Neuroscience.2002,113(3):683-687.
[79]Valable S, Montaner J, Bellail A, et al. VEGF-induced BBB permeability isassociated with an MMP-9activity increase in cerebral ischemia: both effectsdecreased by Ang-1[J]. J Cereb Blood Flow Metab.2005,25(11):1491-1504.
[80]Dayoub H, Achan V, Adimoolam S, et al. Dimethylargininedimethylaminohydrolase regulates nitric oxide synthesis: genetic and physiologicalevidence [J]. Circulation.2003,108(24):3042-3047.
[81]Dayoub H, Rodionov R, Lynch C, et al. Overexpression of dimethylargininedimethylaminohydrolase inhibits asymmetric dimethylarginine-induced endothelialdysfunction in the cerebral circulation [J]. Stroke.2008,39(1):180-184.
[82]Tran CT, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway [J]. AtherosclerSuppl.2003,4(4):33-40.
[83]Pluta RM. Dysfunction of nitric oxide synthases as a cause and therapeutic target indelayed cerebral vasospasm after SAH [J]. Neurol Res.2006,28(7):730-737.
[84]Goll DE, Thompson VF, Li H, et al. The calpain system [J]. Physiol Rev.2003,83(3):731-801.
[85]Lee KS, Yanamoto H, Fergus A, et al. Calcium-activated proteolysis as atherapeutic target in cerebrovascular disease [J]. Ann N Y Acad Sci.1997,825:95-103.
[86]Sun M, Zhao Y, Xu C. Cross-talk Between Calpain and Caspase-3in Penumbra andCore During Focal Cerebral Ischemia-reperfusion [J]. Cell Mol Neurobiol.2008,28(1):71-85.
[87]Tsubokawa T, Yamaguchi-Okada M, Calvert JW, et al. Neurovascular and neuronalprotection by E64d after focal cerebral ischemia in rats [J]. J Neurosci Res.2006,84(4):832-840.
[88]Tsubokawa T, Solaroglu I, Yatsushige H, et al. Cathepsin and calpain inhibitor E64dattenuates matrix metalloproteinase-9activity after focal cerebral ischemia in rats[J]. Stroke.2006,37(7):1888-1894.
[89]Vanderklish PW, Bahr BA. The pathogenic activation of calpain: a marker andmediator of cellular toxicity and disease states [J]. Int J Exp Pathol.2000,81(5):323-339.
[90]Germanò A, Costa C, DeFord SM, et al. Systemic administration of a calpaininhibitor reduces behavioral deficits and blood-brain barrier permeability changesafter experimental subarachnoid hemorrhage in the rat [J]. J Neurotrauma.2002,19(7):887-896.
[91]Shoshan-Barmatz V, Gincel D. The voltage-dependent anion channel:characterization, modulation, and role in mitochondrial function in cell life anddeath [J]. Cell Biochem Biophys.2003,39(3):279-292.
[92]Colombini M. VDAC: the channel at the interface between mitochondria and thecytosol [J]. Mol Cell Biochem.2004,256-257(1-2):107-115.
[93]Crompton M, Barksby E, Johnson N, et al. Mitochondrial intermembrane junctionalcomplexes and their involvement in cell death [J]. Biochimie.2002,84(2-3):143-152.
[94]Newmeyer DD, Ferguson-Miller S. Mitochondria: releasing power for life andunleashing the machineries of death [J]. Cell.2003,112(4):481-490.
[95]Shoshan-Barmatz V, Israelson A, Brdiczka D, et al. The voltage-dependent anionchannel (VDAC): function in intracellular signalling, cell life and cell death [J].Curr Pharm Des.2006,12(18):2249-2270.
[96]Shimizu S, Ide T, Yanagida T, et al. Electrophysiological study of a novel large poreformed by Bax and the voltage-dependent anion channel that is permeable tocytochromec [J]. J Biol Chem.2000,275(16):12321-12325.
[97]Baines CP, Kaiser RA, Sheiko T, et al. Voltage-dependent anion channels aredispensable for mitochondrial-dependent cell death [J]. Nat Cell Biol.2007,9(5):550-555.
[98]Chang L, Karin M. Mammalian MAP kinase signalling cascades [J]. Nature.2001,410(6824):37-40.
[99]Tournier C, Hess P, Yang DD, et al. Requirement of JNK for stress-inducedactivation of the cytochrome c-mediated death pathway [J]. Science.2000,288(5467):870-874.
[100] Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosisregulation [J]. Oncogene.2004,23(16):2838-2849.
[101] Kusaka G, Ishikawa M, Nanda A, et al. Signaling pathways for early braininjury after subarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2004,24(8):916-25.
[102] Yatsushige H, Ostrowski RP, Tsubokawa T, et al. Role of c-Jun N-terminalkinase in early brain injury after subarachnoid hemorrhage [J]. J Neurosci Res.2007,85(7):1436-48.
[103] Ansar S, Edvinsson L. Subtype activation and interaction of protein kinase Cand mitogen-activated protein kinase controlling receptor expression in cerebralarteries and microvessels after subarachnoid hemorrhage [J]. Stroke.2008,39(1):185-190.
[1] Macdonald RL, Pluta RM, Zhang JH. Cerebral vasospasm after subarachnoidhemorrhage: the emerging revolution [J]. Nat Clin Pract Neurol.2007,3(5):256-263.
[2] Treggiari-Venzi MM, Suter PM, Romand JA. Review of medical prevention ofvasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensivecare [J]. Neurosurgery.2001,48(2):249-262.
[3] Rabinstein AA, Weigand S, Atkinson JL, et al. Patterns of cerebral infarction inaneurysmal subarachnoid hemorrhage [J]. Stroke.2005,36(5):992-997.
[4] Hansen-Schwartz J, Vajkoczy P, Macdonald RL, et al. Cerebral vasospasm: lookingbeyond vasoconstriction [J]. Trends Pharmacol Sci.2007,28(6):252-256.
[5] Sakowitz OW, Unterberg AW. Detecting and treating microvascular ischemia aftersubarachnoid hemorrhage [J]. Curr Opin Crit Care.2006,12(2):103-111.
[6] Sehba FA, Bederson JB. Mechanisms of acute brain injury after subarachnoidhemorrhage [J]. Neurol Res.2006,28(4):381-398.
[7] Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury aftersubarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2006,26(11):1341-1353.
[8] Broderick JP, Brott TG, Duldner JE, et al. Initial and recurrent bleeding are themajor causes of death following subarachnoid hemorrhage [J]. Stroke.1994,25(7):1342-1347.
[9] Schievink WI, Wijdicks EF, Parisi JE, et al. Sudden death from aneurysmalsubarachnoid hemorrhage [J]. Neurology.1995,45(5):871-874.
[10]Jakobsen M. Role of initial brain ischemia in subarachnoid hemorrhage followinganeurysm rupture. A pathophysiological survey [J]. Acta Neurol Scand Suppl.1992,141:1-33.
[11]Roos YB, de Haan RJ, Beenen LF, et al. Complications and outcome in patientswith aneurysmal subarachnoid haemorrhage: a prospective hospital based cohortstudy in the Netherlands [J]. J Neurol Neurosurg Psychiatry.2000,68(3):337-341.
[12]Kamiya K, Kuyama H, Symon L. An experimental study of the acute stage ofsubarachnoid hemorrhage [J]. J Neurosurg.1983,59(6):917-924.
[13]Brinker T, Seifert V, Stolke D. Acute changes in the dynamics of the cerebrospinalfluid system during experimental subarachnoid hemorrhage [J]. Neurosurgery.1990,27(3):369-372.
[14]Brinker T, Seifert V, Dietz H. Cerebral blood flow and intracranial pressure duringexperimental subarachnoid haemorrhage [J]. Acta Neurochir (Wien).1992,115(1-2):47-52.
[15]Grote E, Hassler W. The critical first minutes after subarachnoid hemorrhage [J].Neurosurgery.1988,22(4):654-661.
[16]Jackowski A, Crockard A, Burnstack G, et al. The time course of intracranialpathophysiological changes following experimental subarachnoid hemorrhage inthe rat [J]. J Cereb Blood Flow Metab.1990,10(6):835-839.
[17]Kivisaari RP, Salonen O, Servo A, et al. MR imaging after aneurysmalsubarachnoid hemorrhage and surgery: a long-term follow-up study [J]. AJNR Am JNeuroradiol.2001,22(6):1143-1148.
[18]Dorhout Mees SM, van den Bergh WM, Algra A, et al. Achieved serum magnesiumconcentrations and occurrence of delayed cerebral ischaemia and poor outcome inaneurysmal subarachnoid haemorrhage [J]. J Neurol Neurosurg Psychiatry.2007,78(7):729-731.
[19]Jarus-Dziedzic K, Juniewicz H, Wro ski J, et al. The relation between cerebralblood flow velocities as measured by TCD and the incidence of delayed ischemicdeficits. A prospective study after subarachnoid hemorrhage [J]. Neurol Res.2002,24(6):582-592.
[20]Weidauer S, Lanfermann H, Raabe A, et al. Impairment of cerebral perfusion andinfarct patterns attributable to vasospasm after aneurysmal subarachnoidhemorrhage: a prospective MRI and DSA study [J]. Stroke.2007,38(6):1831-1836.
[21]Weidauer S, Vatter H, Beck J, et al. Focal laminar cortical infarcts followinganeurysmal subarachnoid haemorrhage [J]. Neuroradiology.2008,50(1):1-8.
[22]Shimoda M, Takeuchi M, Tominaga J, et al. Asymptomatic versus symptomaticinfarcts from vasospasm in patients with subarachnoid hemorrhage: serial magneticresonance imaging [J]. Neurosurgery.2001,49(6):1341-1348.
[23]Stein SC, Browne KD, Chen XH, et al. Thromboembolism and delayed cerebralischemia after subarachnoid hemorrhage: an autopsy study [J]. Neurosurgery.2006,59(4):781-787.
[24]Dreier JP, Sakowitz OW, Harder A, et al. Focal laminar cortical MR signalabnormalities after subarachnoid hemorrhage [J]. Ann Neurol.2002,52(6):825–829.
[25]Dreier JP, Woitzik J, Fabricius M, et al. Delayed ischaemic neurological deficitsafter subarachnoid haemorrhage are associated with clusters of spreadingdepolarizations [J]. Brain.2006,129(Pt12):3224-3237.
[26]Del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia [J]. JCereb Blood Flow Metab.2003,23(8):879-894.
[27]Perkins E, Kimura H, Parent AD, et al. Evaluation of the microvasculature andcerebral ischemia after experimental subarachnoid hemorrhage in dogs [J]. JNeurosurg.2002,97(4):896-904.
[28]Ohkuma H, Itoh K, Shibata S, et al. Morphological changes of intraparenchymalarterioles following experimental subarachnoid hemorrhage in dogs [J].Neurosurgery.1997,41(1):230–236.
[29]Ohkuma H, Suzuki S. Histological dissociation between intra-andextraparenchymal portion of perforation small arteries after experimentalsubarachnoid hemorrhage in dogs [J]. Acta Neuropathol.1999,98:374-382.
[30]Uhl E, Lehmberg J, Steiger HJ, et al. Intraoperative detection of earlymicrovasospasm in patients with subarachnoid hemorrhage by using orthogonalpolarization spectral imaging [J]. Neurosurgery.2003,52(6):1307-1317.
[31]Pennings FA, Bouma GJ, Ince C. Direct observation of the human cerebralmicrocirculation during aneurysm surgery reveals increased arteriolar contractility[J]. Stroke.2004,35(6):1284-1288.
[32]Ohkuma H, Manabe H, Tanaka M, et al. Impact of cerebral microcirculatorychanges on cerebral blood flow during cerebral vasospasm after subarachnoidhemorrhage [J]. Stroke.2000,31(7):1621–1627.
[33]刘承基,编著.脑血管外科学[M].南京:江苏科学技术出版社.1999,10-21.
[34]Rasmussen G, Hauerberg J, Waldemar G, et al. Cerebral blood flow autoregulationin experimental subarachnoid haemorrhage in rat [J]. Acta Neurochir (Wien).1992,119(1-4):128–133
[35]Ebel H, Rust DS, Leschinger A, et al. Vasomotion, regional cerebral blood flow andintracranial pressure after induced subarachnoid haemorrhage in rats [J]. ZentralblNeurochir.1996,57(3):150–155
[36]Yundt KD, Grubb RL Jr, Diringer MN, et al. Autoregulatory vasodilation ofparenchymal vessels is impaired during cerebral vasospasm [J]. J Cereb BloodFlow Metab.1998,18(4):419-424.
[37]Park KW, Metais C, Dai HB, et al. Microvascular endothelial dysfunction and itsmechanism in a rat model of subarachnoid hemorrhage [J]. Anesth Analg.2001,92(4):990-996.
[38]Kozniewska E, Michalik R, Rafalowska J, et al. Mechanisms of vasculardysfunction after subarachnoid hemorrhage [J]. J Physiol Pharmacol.2006,57(suppl11):145-160.
[39]Yamamoto S, Nishizawa S, Tsukada H, et al. Cerebral autoregulation followingsubarachnoid hemorrhage in rats: chronic vasospasm shifts the upper and lowerlimits of the autoregulatory range toward higher blood pressure [J]. Brain Res.1998,782(1-2):194-201.
[40]Asano T, Sano K. Pathogenetic role of no-reflow phenomenon in experimentalsubarachnoid hemorrhage in dogs [J]. J Neurosurg.1977,46(4):454–466.
[41]Sehba FA, Mostafa G, Knopman J, et al. Acute alterations in microvascular basallamina after subarachnoid hemorrhage [J]. J Neurosurg.2004,101(4):633-640.
[42]Sehba FA, Mustafa G, Friedrich V, et al. Acute microvascular platelet aggregationafter subarachnoid hemorrhage [J]. J Neurosurg.2005,102(6):1094-1100.
[43]Naredi S, Lambert G, Eden E, et al. Increased sympathetic nervous activity inpatients with nontraumatic subarachnoid hemorrhage [J]. Stroke.2000,31(4):901-906.
[44]Schwartz AY, Sehba FA, Bederson JB. Decreased nitric oxide availabilitycontributes to acute cerebral ischemia after subarachnoid hemorrhage [J].Neurosurgery.2000,47(1):208-214.
[45]Sehba FA, Schwartz AY, Chereshnev I, et al. Acute decrease in cerebral nitric oxidelevels after subarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2000,20(3):604-611.
[46]Lambert E, Lambert G, Fassot C, et al. Subarachnoid hemorrhage inducedsympathoexcitation arises due to changes in endothelin and/or nitric oxide activity[J]. Cardiovasc Res.2000,45(4):1046-1053.
[47]Johshita H, Kassell NF, Sasaki T. Blood-brain barrier disturbance followingsubarachnoid haemorrhage in rabbits [J]. Stroke.1990,21(7):1051-1058.
[48]Germano A, d’Avella D, Imperatore C, et al. Time-course of blood brain barrierpermeability changes after experimental subarachnoid hemorrhage [J]. ActaNeurochir (Wien).2000,142(5):575-581.
[49]Imperatore C, Germano A, d'Avella D, et al. Effects of the radical scavanger AVSon behavioral and BBB changes after experimental subarachnoid hemorrhage [J].Life Sci.2000,66(9):779-790.
[50]Sercombe R, Dinh Y R, Gomis P. Cerebrovascular inflammation followingsubarachnoid hemorrhage [J]. Jpn J Pharmacol.2002,88(3):227-249.
[51]Gules I, Satoh M, Nanda A, et al. Apoptosis, blood–brain barrier, andsubarachnoid hemorrhage [J]. Acta Neurochir Suppl.2003,86:483-487.
[52]Cahill J, Calvert JW, Marcantonio S, et al. p53may play an orchestrating role inapoptotic cell death after experimental subarachnoid hemorrhage [J]. Neurosurgery.2007,60(3):531-545.
[53]Park S, Yamaguchi M, Zhou C, et al. Neurovascular protection reduces early braininjury after subarachnoid hemorrhage [J]. Stroke.2004,35(10):2412-2417.
[54]Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injuryafter subarachnoid hemorrhage [J]. Neurol Res.2006,28(4):399-414.
[55]Claassen J, Carhuapoma JR, Kreiter KT, et al. Global cerebral edema aftersubarachnoid hemorrhage: frequency, predictors, and impact on outcome [J]. Stroke.2002,33(5):1225-1232.
[56]Mocco J, Prickett CS, Komotar RJ, et al. Potential mechanisms and clinicalsignificance of global cerebral edema following aneurysmal subarachnoidhemorrhage [J]. Neurosurg Focus.2007,22(5): E7.
[2] Hansen-Schwartz J, Vajkoczy P, Macdonald RL, et al. Cerebral vasospasm: lookingbeyond vasoconstriction [J]. Trends Pharmacol Sci.2007,28(6):252-256.
[3] Sehba FA, Bederson JB. Mechanisms of acute brain injury after subarachnoidhemorrhage [J]. Neurol Res.2006,28(4):381-398.
[4] Prunell GF, Mathiesen T, Svendgaard NA. A new experimental model in rats forstudy of the pathophysiology of subarachnoid hemorrhage [J]. Neuroreport.2002,13(18):2553-2556.
[5] Schwartz AY, Masago A, Sehba FA, et al. Experimental models of subarachnoidhemorrhage in the rat: a refinement of the endovascular filament model [J]. JNeurosci Methods.2000,96(2):161-167.
[6] Bederson JB，Germano IM，Guarino L．Cortical blood flow and cerebral perfusionpressure in a new noncraniotomy model of subarachnoid hemorhage in the rat [J].Stroke, l995,26(6): l086-1092.
[7] Megyesi JF, Vollrath B, Cook DA, et al. In vivo animal models of cerebralvasospasm: A review [J]. Neurosurgery.2000,46(2):448-461.
[8] Velthuis BK, Rinkel GJ, Ramos LM, et al. Subarachnoid hemorrhage: aneurysmdetection and preoperative evaluation with CT angiography [J]. Radiology.1998,208(2):423-430.
[9] Xi G, Hua Y, Keep RF, et al. Brain edema after intracerebral hemorrhage: the effectsof systemic complement depletion [J]. Acta Neurochir Suppl.2002,81:253–256.
[10]Uyama O, Okamura N, Yanase M, et al. Quantitative evaluation of vascularpermeability in the gerbil brain after transient ischemia using Evans bluefluorescence [J]. J Cereb Blood Flow Metab.1988,8(2):282-284.
[11]Bertram KJ, Shipley MT, Ennis M, et al. Permeability of the blood-brain barrierwithin rat intrastriatal transplants assessed by simultaneous systemic injection ofhorseradish peroxidase and Evans blue dye [J]. Exp Neurol.1994,127(2):245-252.
[12]Saria A, Lundberg JM. Evans blue fluorescence: Quantitative and morphologicalevaluation of vascular permeability in animal tissues [J]. J Neurosci Methods.1983,8(1):81-89.
[13]Belayev L, Brsto R, Zhao W, et al. Quantitative evaluation of blood-brain barrierpermeability following middle cerebral artery occlusion in rats [J]. Brain Res.1996,739(1):88-96.
[14]邝芳,王百忍,王凌,等.利用伊文思蓝的荧光显示肾上腺素诱发的血脑屏障开放[J].神经解剖学杂志.1997,13(4):417-420.
[15]Carrera RM, Pacheco AM Jr, Mastroti RA. Qualitative evaluation of theblood-brain barrier after the use of hypertonic saline solution in young rats [J]. EurSurg Res.2001,33(5-6):311-317.
[16]Germano A, d’Avella D, Imperatore C, et al. Time-course of blood brain barrierpermeability changes after experimental subarachnoid hemorrhage [J]. ActaNeurochir (Wien).2000,142(5):575-581.
[17]Fischer S, Wobben M, Marti HH, et al. Hypoxia-induced hyperpermeability in brainmicrovessel endothelial cells involves VEGF-mediated changes in the expression ofzonula occludens-1[J]. Microvasc Res.2002,63(1):70-80.
[18]Krizbai IA, Deli MA. Signalling pathways regulating the tight junctionpermeability in the blood-brain barrier [J]. Cell Mol Biol (Noisy-le-grand).2003,49(1):23-31.
[19]Abbott NJ. Astrocyte-endothelial interactions and blood-brain barrier permeability[J]. J Anat.2002,200(6):629-38.
[20]Li YQ, Chen P, Haimovitz-Friedman A, et al. Endothelial apoptosis initiates acuteblood-brain barrier disruption after ionizing radiation [J]. Cancer Res.2003,63(18):5950-5956.
[21]Stewart PA. Endothelial vesicles in the blood-brain barrier: are they related topermeability?[J]. Cell Mol Neurobiol.2000,20(2):149-163.
[22]Doczi T. The pathogenetic and prognostic significance of blood-brain barrierdamage at the acute stage of aneurismal subarachnoid haemorrhage. Clinical andexperimental studies [J]. Acta Neurochir (Wien).1985,77(3-4):110-132.
[23]Trojanowski T. Blood-brain barrier changes after experimental subarachnoidhaemorrhage [J]. Acta Neurochir (Wien).1982,60(1-2):45-54.
[24]Doczi T, Joo F, Adam G, et al. Blood-brain barrier damage during the acute stage ofsubarachnoid hemorrhage, as exemplified by a new animal model [J]. Neurosurgery.1986,18(6):733-739.
[25]Jacowski A, Crockard A, Burnstock G, et al. The time course of intracranialpathophysiological changes following experimental subarachnoid haemorrhage inthe rat [J]. J Cereb Blood Flow Metab.1990,10(6):835–849.
[26]d’Avella D, Cicciarello R, Zuccarello M, et al. Brain energy metabolism in theacute stage of experimental subarachnoid haemorrhage: local changes in cerebralglucose utilization [J]. Acta Neurochir (Wien).1996,138(6):737–744.
[27]Imperatore C, Germano A, d'Avella D, et al. Effects of the radical scavanger AVSon behavioral and BBB changes after experimental subarachnoid haemorrhage [J].Life Sciences.2000,66(9):779-790.
[28]Sehba FA, Mostafa G, Knopman J, et al. Acute alterations in microvascular basallamina after subarachnoid hemorrhage [J]. J Neurosurg.2004,101(4):633–640.
[29]Mayhan WG. VEGF increases permeability of the blood-brain barrier via a nitricoxide synthase/cGMP-dependent pathway [J]. Am J Physiol.1999,276(5):C1148–C53.
[30]Kusaka G, Ishikawa M, Nanda A, et al. Signaling pathways for early brain injuryafter subarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2004,24(8):916–25.
[31]Sercombe R, Dinh YR, Gomis P. Cerebrovascular inflammation followingsubarachnoid hemorrhage [J]. Jpn J Pharmacol.2002,88(3):227–249
[32]Yatsushige H, Ostrowski RP, Tsubokawa T, et al. Role of c-Jun N-terminal kinase inearly brain injury after subarachnoid hemorrhage [J]. J Neurosci Res.2007,85(7):1436-1448.
[33]Cahill J, Calvert JW, Marcantonio S, et al. p53may play an orchestrating role inapoptotic cell death after experimental subarachnoid hemorrhage [J]. Neurosurgery.2007,60(3):531-545.
[34]Park S, Yamaguchi M, Zhou C, et al. Neurovascular protection reduces early braininjury after subarachnoid hemorrhage [J]. Stroke.2004,35(10):2412–2417.
[35]Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injuryafter subarachnoid hemorrhage [J]. Neurol Res.2006,28(4):399–414.
[36]Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury aftersubarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2006,26(11):1341-1353.
[37]Claassen J, Carhuapoma JR, Kreiter KT, et al. Global cerebral edema aftersubarachnoid hemorrhage: frequency, predictors, and impact on outcome [J]. Stroke.2002,33(5):1225-1232.
[38]Mocco J, Prickett CS, Komotar RJ, et al. Potential mechanisms and clinicalsignificance of global cerebral edema following aneurysmal subarachnoidhemorrhage [J]. Neurosurg Focus.2007,22(5): E7.
[39]Germanò A, Caffo M, Angileri FF et al. NMDA receptor antagonist felbamatereduces behavioral deficits and blood-brain barrier permeability changes afterexperimental subarachnoid hemorrhage in the rat [J]. J Neurotrauma.2007,24(4):732-744.
[1] Abbort A. And now for the proteome [J]. Nature.2001,409(6822):747.
[2] Tyers M, Mann M. From genomics to proteomics [J]. Nature.2003,422(6928):193-197.
[3] Sali A, Glaeser R, Earnest T, et al. From words to literature in structural proteomics[J]. Nature.2003,422(6928):216-225.
[4] Aittokallio T, Salmi J, Nyman TA, et al. Geometrical distortions in two-dimensionalgels: applicable correction methods [J]. J Chromatogr B Analyt Technol BiomedLife Sci.2005,815(1-2):25-37.
[5] The Protocol Guide for Leica Laser Microdissection Systems.http://www.leica-microsystems.com.
[6] Boado RJ, Pardridge WM. A one-step procedure for isolation of poly(A)+mRNAfrom isolated brain capillaries and endothelial cells in culture [J]. J Neurochem.1991,57(6):2136–2139.
[7] Yousif S, Marie-Claire C, Roux F, et al. Expression of drug transporters at theblood-brain barrier using an optimized isolated rat brain microvessel strategy [J].Brain Res.2007,1134(1):1-11.
[8] Calabria AR, Shusta EV. Blood-brain barrier genomics and proteomics: elucidatingphenotype, identifying disease targets and enabling brain drug delivery [J]. DrugDiscov Today.2006,11(17-18):792-799.
[9] Emmert-Buck MR, Bonner RF, Smith PD, et al. Laser capture microdissection [J].Science.1996,274(5289):998-1001.
[10]Espina V, Milia J, Wu G, et al. Laser capture microdissection [J]. Methods Mol Biol.2006,319:213-229.
[11]Simone NL, Bonner RF, Gillespie JW, et al. Laser-capture microdissection:opening the microscopic frontier to molecular analysis [J]. Trends Genet.1998,14(7):272-276.
[12]Espina V, Heiby M, Pierobon M, et al. Laser capture microdissection technology[J]. Expert Rev Mol Diagn.2007,7(5):647-657.
[13]Xu C, Houck JR, Fan W, et al. Simultaneous Isolation of DNA and RNA from theSame Cell Population Obtained by Laser Capture Microdissection for Genome andTranscriptome Profiling [J]. J Mol Diagn.2008,10(2):129-134.
[14]Espina V, Wulfkuhle JD, Calvert VS, et al. Laser-capture microdissection [J]. NatProtoc.2006,1(2):586-603.
[15]von Eggeling F, Melle C, Ernst G. Microdissecting the proteome [J]. Proteomics.2007,7(16):2729-2737.
[16] Ball HJ, McParland B, Driussi C, et al. Isolating vessels from the mouse brain forgene expression analysis using laser capture microdissection [J]. Brain Res BrainRes Protoc.2002,9(3):206-213.
[17]Craven RA, Totty N, Harnden P, et al. Laser capture microdissection andtwo-dimensional polyacrylamide gel electrophoresis: evaluation of tissuepreparation and sample limitations [J]. Am J Pathol.2002,160(3):815-822.
[18]Fend F, Emmert-Buck MR, Chuaqui R, et al. Immuno-LCM: laser capturemicrodissection of immunostained frozen sections for mRNA analysis [J]. Am JPathol.1999,154(1):61-66.
[19]Moulédous L, Hunt S, Harcourt R, et al. Proteomic analysis of immunostained,laser-capture microdissected brain samples [J]. Electrophoresis.2003,24(1-2):296-302.
[20]De Souza AI, McGregor E, Dunn MJ, et al. Preparation of human heart for lasermicrodissection and proteomics [J]. Proteomics.2004,4(3):578-586.
[21]Leverenz JB, Umar I, Wang Q, et al. Proteomic identification of novel proteins incortical lewy bodies [J]. Brain Pathol.2007,17(2):139-145.
[22]Moulédous L, Hunt S, Harcourt R, et al. Navigated laser capture microdissection asan alternative to direct histological staining for proteomic analysis of brain samples[J]. Proteomics.2003,3(5):610-615.
[23]Gutstein HB, Morris JS. Laser capture sampling and analytical issues in proteomics[J]. Expert Rev Proteomics.2007,4(5):627-637.
[24]陈主初,梁宋平等.肿瘤蛋白质组学[M].湖南科学技术出版社.2002,23-24.
[25]G rg A, Weiss W, Dunn MJ. Current two-dimensional electrophoresis technologyfor proteomics [J]. Proteomics.2004,4(12):3665-3685.
[26]G rg A, Obermaier C, Boguth G, et al. The current state of two-dimensionalelectrophoresis with immobilized pH gradients [J]. Electrophoresis.2000,21(6):1037-1053.
[27]Herbert BR, Molloy MP, Gooley AA, et al. Improved protein solubility intwo-dimensional electrophoresis using tributyl phosphine as reducing agent [J].Electrophoresis.1998,19(5):845-851.
[28]夏其昌,曾嵘等.蛋白质化学与蛋白质组学[M].科学出版社.2004,271-274.
[29]Celis JE, Carter N, Hunter T, et al. Protein detection in gels by silver staining：aprocedure compatible with mass-spectrometry. Cell Biology: a laboratoryhandbook(3rd Edition)[M]. Elsevier. Academic Press.2006.219-223.
[1] van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage [J]. Lancet.2007,369(9558):306-318.
[2] Kozniewska E, Michalik R, Rafalowska J, et al. Mechanisms of vasculardysfunction after subarachnoid hemorrhage [J]. J Physiol Pharmacol.2006,57(suppl11):145-160.
[3] Sehba FA, Bederson JB. Mechanisms of acute brain injury after subarachnoidhemorrhage [J]. Neurol Res.2006,28(4):381-98.
[4] Claassen J, Carhuapoma JR, Kreiter KT, et al. Global cerebral edema aftersubarachnoid hemorrhage: frequency, predictors, and impact on outcome [J]. Stroke.2002,33(5):1225-1232.
[5] Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injuryafter subarachnoid hemorrhage [J]. Neurol Res.2006,28(4):399-414.
[6] Mocco J, Prickett CS, Komotar RJ, et al. Potential mechanisms and clinicalsignificance of global cerebral edema following aneurysmal subarachnoidhemorrhage [J]. Neurosurg Focus.2007,22(5): E7.
[7] Ohkuma H, Manabe H, Tanaka M, et al. Impact of cerebral microcirculatorychanges on cerebral blood flow during cerebral vasospasm after aneurysmalsubarachnoid hemorrhage [J]. Stroke.2000,31(7):1621-1627.
[8] Tyers M, Mann M. From genomics to proteomics [J]. Nature.2003,422(6928):193-197.
[9] Paulson L, Martin P, Persson A, et al. Comparative genome-and proteome analysisof cerebral cortex from MK-801-treated rats [J]. J Neurosci Res.2003,71(4):526-533.
[10]Shevchenko A, Tomas H, Havlis J, et al. In-gel digestion for mass spectrometriccharacterization of proteins and proteomes [J]. Nat Protoc.2006,1(6):2856-2860.
[11]Macdonald RL, Pluta RM, Zhang JH. Cerebral vasospasm after subarachnoidhemorrhage: the emerging revolution [J]. Nat Clin Pract Neurol.2007,3(5):256-263.
[12]Treggiari-Venzi MM, Suter PM, Romand JA. Review of medical prevention ofvasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensivecare [J]. Neurosurgery.2001,48(2):249-262.
[13]Rabinstein AA, Friedman JA, Weigand SD, et al. Predictors of cerebral infarction inaneurysmal subarachnoid hemorrhage [J]. Stroke.2004,35(8):1862–1866.
[14]Rabinstein AA, Weigand S, Atkinson JL, et al. Patterns of cerebral infarction inaneurysmal subarachnoid hemorrhage [J]. Stroke.2005,36(5):992–997.
[15]Del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia [J]. JCereb Blood Flow Metab.2003,23(8):879-894.
[16][16] Uhl E, Lehmberg J, Steiger HJ, et al. Intraoperative detection of earlymicrovasospasm in patients with subarachnoid hemorrhage by using orthogonalpolarization spectral imaging [J]. Neurosurgery.2003,52(6):1307-1317.
[17]Pennings FA, Bouma GJ, Ince C. Direct observation of the human cerebralmicrocirculation during aneurysm surgery reveals increased arteriolar contractility[J]. Stroke.2004,35(6):1284-1288.
[18]Yamamoto S, Nishizawa S, Tsukada H, et al. Cerebral autoregulation followingsubarachnoid hemorrhage in rats: chronic vasospasm shifts the upper and lowerlimits of the autoregulatory range toward higher blood pressure [J]. Brain Res.1998,782(1-2):194-201.
[19]Weidauer S, Vatter H, Beck J, et al. Focal laminar cortical infarcts followinganeurysmal subarachnoid haemorrhage [J]. Neuroradiology.2008,50(1):1-8.
[20]Sehba FA, Mostafa G, Friedrich V, et al. Acute microvascular platelet aggregationafter subarachnoid hemorrhage [J]. J Neurosurg.2005,102(6):1094–1100.
[21]Sehba FA, Mostafa G, Knopman J, et al. Acute alterations in microvascular basallamina after subarachnoid hemorrhage [J]. J Neurosurg.2004,101(4):633-40.
[22]Sehba FA, Friedrich V Jr, Makonnen G, et al. Acute cerebral vascular injury aftersubarachnoid hemorrhage and its prevention by administration of a nitric oxidedonor [J]. J Neurosurg.2007,106(2):321-329.
[23]Sch ller K, Trinkl A, Klopotowski M, et al. Characterization of microvascularbasal lamina damage and blood-brain barrier dysfunction following subarachnoidhemorrhage in rats [J]. Brain Res.2007,1142:237-246.
[24]Lassalle P, Molet S, Janin A, et al. ESM-1is a novel human endothelial cell-specificmolecule expressed in lung and regulated by cytokines [J]. J Biol Chem.1996,271(34):20458-20464.
[25]Bechard D, Meignin V, Scherpereel A, et al. Characterization of the secreted formof endothelial-cell-specific molecule1by specific monoclonal antibodies [J]. J VascRes.2000,37(5):417-425.
[26]Sarrazin S, Adam E, Lyon M, et al. Endocan or endothelial cell specific molecule-1(ESM-1): a potential novel endothelial cell marker and a new target for cancertherapy [J]. Biochim Biophys Acta.2006,1765(1):25-37.
[27]van Gurp M, Festjens N, van Loo G, et al. Mitochondrial intermembrane proteins incell death [J]. Biochem Biophys Res Commun.2003,304(3):487-497.
[28]Jensen RE, Dunn CD. Protein import into and across the mitochondrial innermembrane: role of the TIM23and TIM22translocons [J]. Biochim Biophys Acta.2002,1592(1):25-34.
[29]Kutik S, Guiard B, Meyer HE, et al. Cooperation of translocase complexes inmitochondrial protein import [J]. J Cell Biol.2007,179(4):585-591.
[30]Morimoto RI. Cells in stress: transcriptional activation of heat shock genes [J].Science.1993,259(5100):1409-1410.
[31]Haslbeck M. sHsps and their role in the chaperone network [J]. Cell Mol Life Sci.2002,59(10):1649-1657.
[32]David JC, Boelens WC, Grongnet JF. Up-regulation of heat shock protein HSP20in the hippocampus as an early response to hypoxia of the newborn [J]. JNeurochem.2006,99(2):570-581.
[33]Smith SL, Scherch HM, Hall ED. Protective effects of tirilazad mesylate andmetabolite U-89678against blood-brain barrier damage after subarachnoidhemorrhage and lipid peroxidative neuronal injury [J]. J Neurosurg.1996,84(2):229-233.
[34]Sen O, Caner H, Aydin MV, et al. The effect of mexiletine on the level of lipidperoxidation and apoptosis of endothelium following experimental subarachnoidhemorrhage [J]. Neurol Res.2006,28(8):859-863.
[35]Ostrowski RP, Tang J, Zhang JH. Hyperbaric oxygen suppresses NADPH oxidasein a rat subarachnoid hemorrhage model [J]. Stroke.2006,37(5):1314-1318.
[36]Nilius B, Droogmans G. Amazing chloride channels: an overview [J]. Acta PhysiolScand.2003,177(2):119-147.
[37]Suh KS, Mutoh M, Nagashima K, et al. The organellular chloride channel proteinCLIC4/mtCLIC translocates to the nucleus in response to cellular stress andaccelerates apoptosis [J]. J Biol Chem.2004,279(6):4632-4641.
[38]Suh KS, Mutoh M, Gerdes M, et al. CLIC4, an intracellular chloride channelprotein, is a novel molecular target for cancer therapy [J]. J Investig DermatolSymp Proc.2005,10(2):105-109.
[39]Suginta W, Karoulias N, Aitken A, et al. Chloride intracellular channel proteinCLIC4(p64H1) binds directly to brain dynamin I in a complex containing actin,tubulin and14-3-3isoforms [J]. Biochem J.2001,359(Pt1):55-64.
[40]Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury aftersubarachnoid hemorrhage [J]. J Cereb Blood Flow Metab,2006,26(11):1341-1353.
[41]Zhou C, Yamaguchi M, Kusaka G, et al. Caspase inhibitors prevent endothelialapoptosis and cerebral vasospasm in dog model of experimental subarachnoidhemorrhage [J]. J Cereb Blood Flow Metab.2004,24(4):419–431.
[42]Park S, Yamaguchi M, Zhou C, et al. Neurovascular protection reduces early braininjury after subarachnoid hemorrhage [J]. Stroke.2004,35(10):2412–2417.
[43]Hawkins TE, Merrifield CJ, Moss SE. Calcium signaling and annexins [J]. CellBiochem Biophys.2000,33(3):275-296.
[44]Gerke V, Moss SE. Annexins: from structure to function [J]. Physiol Rev.2002,82(2):331-371.
[45]Hayes MJ, Moss SE. Annexins and disease [J]. Biochem Biophys Res Commun.2004,322(4):1166-1170.
[46]Reutelingsperger CP. Annexins: key regulators of haemostasis, thrombosis, andapoptosis [J]. Thromb Haemost.2001,86(1):413-419.
[47]Boersma HH, Kietselaer BL, Stolk LM, et al. Past, present, and future of annexinA5: from protein discovery to clinical applications [J]. J Nucl Med.2005,46(12):2035-2050.
[48]Kenis H, Hofstra L, Reutelingsperger CP. Annexin A5: shifting from a diagnostictowards a therapeutic realm [J]. Cell Mol Life Sci.2007,64(22):2859-2862.
[49]Nicholl SM, Roztocil E, Davies MG. Plasminogen activator system and vasculardisease [J]. Curr Vasc Pharmacol.2006,4(2):101-116.
[50]Lindgren A, Lindoff C, Norrving B, et al. Tissue plasminogen activator andplasminogen activator inhibitor-1in stroke patients [J]. Stroke.1996,27(6):1066-1071.
[51]Peltonen S, Juvela S, Kaste M, et al. Hemostasis and fibrinolysis activation aftersubarachnoid hemorrhage [J]. J Neurosurg.1997,87(2):207-214.
[52]Vergouwen MD, Frijns CJ, Roos YB, et al. Plasminogen activator inhibitor-14Gallele in the4G/5G promoter polymorphism increases the occurrence of cerebralischemia after aneurysmal subarachnoid hemorrhage [J]. Stroke.2004,35(6):1280-1283.
[53]Roos YB, Levi M, Carroll TA, et al. Nimodipine increases fibrinolytic activity inpatients with aneurysmal subarachnoid hemorrhage [J]. Stroke.2001,32(8):1860-1862.
[54]Blalock JE. A molecular basis for bidirectional communication between theimmune and neuroendocrine systems [J]. Physiol Rev.1989,69(1):1-32.
[55]Basu A, Krady JK, Levison SW. Interleukin-1: a master regulator ofneuroinflammation [J]. J Neurosci Res.2004,78(2):151-156.
[56]Pinteaux E, Rothwell NJ, Boutin H. Neuroprotective actions of endogenousinterleukin-1receptor antagonist (IL-1ra) are mediated by glia [J]. Glia.2006,53(5):551-556.
[57]Towne JE, Garka KE, Renshaw BR, et al. Interleukin (IL)-1F6, IL-1F8, and IL-1F9signal through IL-1Rrp2and IL-1RAcP to activate the pathway leading toNF-kappaB and MAPKs [J]. J Biol Chem.2004,279(14):13677-13688.
[58]Li X, Stark GR. NFkappaB-dependent signaling pathways [J]. Exp Hematol.2002,30(4):285-296.
[59]Gallia GL, Tamargo RJ. Leukocyte-endothelial cell interactions in chronicvasospasm after subarachnoid hemorrhage [J]. Neurol Res.2006,28(7):750-758.
[60]Abbott NJ. Inflammatory mediators and modulation of blood-brain barrierpermeability [J]. Cell Mol Neurobiol.2000,20(2):131-147.
[61]Fassbender K, Hodapp B, Rossol S, et al. Inflammatory cytokines in subarachnoidhaemorrhage: association with abnormal blood flow velocities in basal cerebralarteries [J]. J Neurol Neurosurg Psychiatry.2001,70(4):534-537.
[62]Sercombe R, Dinh YR, Gomis P. Cerebrovascular inflammation followingsubarachnoid hemorrhage [J]. Jpn J Pharmacol.2002,88(3):227-249.
[63]Dean DC, Iademarco MF, Rosen GD, et al. The integrin alpha4beta1and itscounter receptor VCAM-1in development and immune function [J]. Am RevRespir Dis.1993,148(6Pt2): S43-46.
[64]Newman PJ, Berndt MC, Gorski J, et al. PECAM-1(CD31) cloning and relation toadhesion molecules of the immunoglobulin gene superfamily [J]. Science.1990,247(4947):1219-1222.
[65]Woodfin A, Voisin MB, Nourshargh S. PECAM-1: a multi-functional molecule ininflammation and vascular biology [J]. Arterioscler Thromb Vasc Biol.2007,27(12):2514-2523.
[66]Kaynar MY, Tanriverdi T, Kafadar AM, et al. Detection of soluble intercellularadhesion molecule-1and vascular cell adhesion molecule-1in both cerebrospinalfluid and serum of patients after aneurysmal subarachnoid hemorrhage [J]. JNeurosurg.2004,101(6):1030-1036.
[67]Rothoerl RD, Schebesch KM, Kubitza M, et al. ICAM-1and VCAM-1expressionfollowing aneurysmal subarachnoid hemorrhage and their possible role in thepathophysiology of subsequent ischemic deficits [J]. Cerebrovasc Dis.2006,22(2-3):143-149.
[68]Rothoerl RD, Ringel F. Molecular mechanisms of cerebral vasospasm followinganeurysmal SAH [J]. Neurol Res.2007,29(7):636-642.
[69]Nissen JJ, Mantle D, Gregson B, et al. Serum concentration of adhesion moleculesin patients with delayed ischaemic neurological deficit after aneurysmalsubarachnoid haemorrhage: the immunoglobulin and selectin superfamilies [J]. JNeurol Neurosurg Psychiatry.2001,71(3):329-333.
[70]Yancopoulos GD, Klagsbrun M, Folkman J. Vasculogenesis, angiogenesis, andgrowth factors: ephrins enter the fray at the border [J]. Cell.1998,93(5):661-664.
[71]Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, andgrowth in tumors mediated by angiopoietins and VEGF [J]. Science.1999,284(5422):1994-1998.
[72]Yancopoulos GD, Davis S, Gale NW, et al. Vascular-specific growth factors andblood vessel formation [J]. Nature.2000,407(6801):242-248.
[73]Lin TN, Wang CK, Cheung WM, et al. Induction of angiopoietin and Tie receptormRNA expression after cerebral ischemia-reperfusion [J]. J Cereb Blood FlowMetab.2000,20(2):387-395.
[74]Zhang Z, Chopp M. Vascular endothelial growth factor and angiopoietins in focalcerebral ischemia [J]. Trends Cardiovasc Med.2002,12(2):62-66.
[75]Zhang ZG, Zhang L, Tsang W, et al. Correlation of VEGF and angiopoietinexpression with disruption of blood-brain barrier and angiogenesis after focalcerebral ischemia [J]. J Cereb Blood Flow Metab.2002,22(4):379-392.
[76]Zhu Y, Lee C, Shen F, et al. Angiopoietin-2facilitates vascular endothelial growthfactor-induced angiogenesis in the mature mouse brain [J]. Stroke.2005,36(7):1533-1537.
[77]Nag S, Papneja T, Venugopalan R, et al. Increased angiopoietin2expression isassociated with endothelial apoptosis and blood-brain barrier breakdown [J]. LabInvest.2005,85(10):1189-1198.
[78]Zhang ZG, Zhang L, Croll SD, Chopp M. Angiopoietin-1reduces cerebral bloodvessel leakage and ischemic lesion volume after focal cerebral embolic ischemia inmice [J]. Neuroscience.2002,113(3):683-687.
[79]Valable S, Montaner J, Bellail A, et al. VEGF-induced BBB permeability isassociated with an MMP-9activity increase in cerebral ischemia: both effectsdecreased by Ang-1[J]. J Cereb Blood Flow Metab.2005,25(11):1491-1504.
[80]Dayoub H, Achan V, Adimoolam S, et al. Dimethylargininedimethylaminohydrolase regulates nitric oxide synthesis: genetic and physiologicalevidence [J]. Circulation.2003,108(24):3042-3047.
[81]Dayoub H, Rodionov R, Lynch C, et al. Overexpression of dimethylargininedimethylaminohydrolase inhibits asymmetric dimethylarginine-induced endothelialdysfunction in the cerebral circulation [J]. Stroke.2008,39(1):180-184.
[82]Tran CT, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway [J]. AtherosclerSuppl.2003,4(4):33-40.
[83]Pluta RM. Dysfunction of nitric oxide synthases as a cause and therapeutic target indelayed cerebral vasospasm after SAH [J]. Neurol Res.2006,28(7):730-737.
[84]Goll DE, Thompson VF, Li H, et al. The calpain system [J]. Physiol Rev.2003,83(3):731-801.
[85]Lee KS, Yanamoto H, Fergus A, et al. Calcium-activated proteolysis as atherapeutic target in cerebrovascular disease [J]. Ann N Y Acad Sci.1997,825:95-103.
[86]Sun M, Zhao Y, Xu C. Cross-talk Between Calpain and Caspase-3in Penumbra andCore During Focal Cerebral Ischemia-reperfusion [J]. Cell Mol Neurobiol.2008,28(1):71-85.
[87]Tsubokawa T, Yamaguchi-Okada M, Calvert JW, et al. Neurovascular and neuronalprotection by E64d after focal cerebral ischemia in rats [J]. J Neurosci Res.2006,84(4):832-840.
[88]Tsubokawa T, Solaroglu I, Yatsushige H, et al. Cathepsin and calpain inhibitor E64dattenuates matrix metalloproteinase-9activity after focal cerebral ischemia in rats[J]. Stroke.2006,37(7):1888-1894.
[89]Vanderklish PW, Bahr BA. The pathogenic activation of calpain: a marker andmediator of cellular toxicity and disease states [J]. Int J Exp Pathol.2000,81(5):323-339.
[90]Germanò A, Costa C, DeFord SM, et al. Systemic administration of a calpaininhibitor reduces behavioral deficits and blood-brain barrier permeability changesafter experimental subarachnoid hemorrhage in the rat [J]. J Neurotrauma.2002,19(7):887-896.
[91]Shoshan-Barmatz V, Gincel D. The voltage-dependent anion channel:characterization, modulation, and role in mitochondrial function in cell life anddeath [J]. Cell Biochem Biophys.2003,39(3):279-292.
[92]Colombini M. VDAC: the channel at the interface between mitochondria and thecytosol [J]. Mol Cell Biochem.2004,256-257(1-2):107-115.
[93]Crompton M, Barksby E, Johnson N, et al. Mitochondrial intermembrane junctionalcomplexes and their involvement in cell death [J]. Biochimie.2002,84(2-3):143-152.
[94]Newmeyer DD, Ferguson-Miller S. Mitochondria: releasing power for life andunleashing the machineries of death [J]. Cell.2003,112(4):481-490.
[95]Shoshan-Barmatz V, Israelson A, Brdiczka D, et al. The voltage-dependent anionchannel (VDAC): function in intracellular signalling, cell life and cell death [J].Curr Pharm Des.2006,12(18):2249-2270.
[96]Shimizu S, Ide T, Yanagida T, et al. Electrophysiological study of a novel large poreformed by Bax and the voltage-dependent anion channel that is permeable tocytochromec [J]. J Biol Chem.2000,275(16):12321-12325.
[97]Baines CP, Kaiser RA, Sheiko T, et al. Voltage-dependent anion channels aredispensable for mitochondrial-dependent cell death [J]. Nat Cell Biol.2007,9(5):550-555.
[98]Chang L, Karin M. Mammalian MAP kinase signalling cascades [J]. Nature.2001,410(6824):37-40.
[99]Tournier C, Hess P, Yang DD, et al. Requirement of JNK for stress-inducedactivation of the cytochrome c-mediated death pathway [J]. Science.2000,288(5467):870-874.
[100] Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosisregulation [J]. Oncogene.2004,23(16):2838-2849.
[101] Kusaka G, Ishikawa M, Nanda A, et al. Signaling pathways for early braininjury after subarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2004,24(8):916-25.
[102] Yatsushige H, Ostrowski RP, Tsubokawa T, et al. Role of c-Jun N-terminalkinase in early brain injury after subarachnoid hemorrhage [J]. J Neurosci Res.2007,85(7):1436-48.
[103] Ansar S, Edvinsson L. Subtype activation and interaction of protein kinase Cand mitogen-activated protein kinase controlling receptor expression in cerebralarteries and microvessels after subarachnoid hemorrhage [J]. Stroke.2008,39(1):185-190.
[1] Macdonald RL, Pluta RM, Zhang JH. Cerebral vasospasm after subarachnoidhemorrhage: the emerging revolution [J]. Nat Clin Pract Neurol.2007,3(5):256-263.
[2] Treggiari-Venzi MM, Suter PM, Romand JA. Review of medical prevention ofvasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensivecare [J]. Neurosurgery.2001,48(2):249-262.
[3] Rabinstein AA, Weigand S, Atkinson JL, et al. Patterns of cerebral infarction inaneurysmal subarachnoid hemorrhage [J]. Stroke.2005,36(5):992-997.
[4] Hansen-Schwartz J, Vajkoczy P, Macdonald RL, et al. Cerebral vasospasm: lookingbeyond vasoconstriction [J]. Trends Pharmacol Sci.2007,28(6):252-256.
[5] Sakowitz OW, Unterberg AW. Detecting and treating microvascular ischemia aftersubarachnoid hemorrhage [J]. Curr Opin Crit Care.2006,12(2):103-111.
[6] Sehba FA, Bederson JB. Mechanisms of acute brain injury after subarachnoidhemorrhage [J]. Neurol Res.2006,28(4):381-398.
[7] Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury aftersubarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2006,26(11):1341-1353.
[8] Broderick JP, Brott TG, Duldner JE, et al. Initial and recurrent bleeding are themajor causes of death following subarachnoid hemorrhage [J]. Stroke.1994,25(7):1342-1347.
[9] Schievink WI, Wijdicks EF, Parisi JE, et al. Sudden death from aneurysmalsubarachnoid hemorrhage [J]. Neurology.1995,45(5):871-874.
[10]Jakobsen M. Role of initial brain ischemia in subarachnoid hemorrhage followinganeurysm rupture. A pathophysiological survey [J]. Acta Neurol Scand Suppl.1992,141:1-33.
[11]Roos YB, de Haan RJ, Beenen LF, et al. Complications and outcome in patientswith aneurysmal subarachnoid haemorrhage: a prospective hospital based cohortstudy in the Netherlands [J]. J Neurol Neurosurg Psychiatry.2000,68(3):337-341.
[12]Kamiya K, Kuyama H, Symon L. An experimental study of the acute stage ofsubarachnoid hemorrhage [J]. J Neurosurg.1983,59(6):917-924.
[13]Brinker T, Seifert V, Stolke D. Acute changes in the dynamics of the cerebrospinalfluid system during experimental subarachnoid hemorrhage [J]. Neurosurgery.1990,27(3):369-372.
[14]Brinker T, Seifert V, Dietz H. Cerebral blood flow and intracranial pressure duringexperimental subarachnoid haemorrhage [J]. Acta Neurochir (Wien).1992,115(1-2):47-52.
[15]Grote E, Hassler W. The critical first minutes after subarachnoid hemorrhage [J].Neurosurgery.1988,22(4):654-661.
[16]Jackowski A, Crockard A, Burnstack G, et al. The time course of intracranialpathophysiological changes following experimental subarachnoid hemorrhage inthe rat [J]. J Cereb Blood Flow Metab.1990,10(6):835-839.
[17]Kivisaari RP, Salonen O, Servo A, et al. MR imaging after aneurysmalsubarachnoid hemorrhage and surgery: a long-term follow-up study [J]. AJNR Am JNeuroradiol.2001,22(6):1143-1148.
[18]Dorhout Mees SM, van den Bergh WM, Algra A, et al. Achieved serum magnesiumconcentrations and occurrence of delayed cerebral ischaemia and poor outcome inaneurysmal subarachnoid haemorrhage [J]. J Neurol Neurosurg Psychiatry.2007,78(7):729-731.
[19]Jarus-Dziedzic K, Juniewicz H, Wro ski J, et al. The relation between cerebralblood flow velocities as measured by TCD and the incidence of delayed ischemicdeficits. A prospective study after subarachnoid hemorrhage [J]. Neurol Res.2002,24(6):582-592.
[20]Weidauer S, Lanfermann H, Raabe A, et al. Impairment of cerebral perfusion andinfarct patterns attributable to vasospasm after aneurysmal subarachnoidhemorrhage: a prospective MRI and DSA study [J]. Stroke.2007,38(6):1831-1836.
[21]Weidauer S, Vatter H, Beck J, et al. Focal laminar cortical infarcts followinganeurysmal subarachnoid haemorrhage [J]. Neuroradiology.2008,50(1):1-8.
[22]Shimoda M, Takeuchi M, Tominaga J, et al. Asymptomatic versus symptomaticinfarcts from vasospasm in patients with subarachnoid hemorrhage: serial magneticresonance imaging [J]. Neurosurgery.2001,49(6):1341-1348.
[23]Stein SC, Browne KD, Chen XH, et al. Thromboembolism and delayed cerebralischemia after subarachnoid hemorrhage: an autopsy study [J]. Neurosurgery.2006,59(4):781-787.
[24]Dreier JP, Sakowitz OW, Harder A, et al. Focal laminar cortical MR signalabnormalities after subarachnoid hemorrhage [J]. Ann Neurol.2002,52(6):825–829.
[25]Dreier JP, Woitzik J, Fabricius M, et al. Delayed ischaemic neurological deficitsafter subarachnoid haemorrhage are associated with clusters of spreadingdepolarizations [J]. Brain.2006,129(Pt12):3224-3237.
[26]Del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia [J]. JCereb Blood Flow Metab.2003,23(8):879-894.
[27]Perkins E, Kimura H, Parent AD, et al. Evaluation of the microvasculature andcerebral ischemia after experimental subarachnoid hemorrhage in dogs [J]. JNeurosurg.2002,97(4):896-904.
[28]Ohkuma H, Itoh K, Shibata S, et al. Morphological changes of intraparenchymalarterioles following experimental subarachnoid hemorrhage in dogs [J].Neurosurgery.1997,41(1):230–236.
[29]Ohkuma H, Suzuki S. Histological dissociation between intra-andextraparenchymal portion of perforation small arteries after experimentalsubarachnoid hemorrhage in dogs [J]. Acta Neuropathol.1999,98:374-382.
[30]Uhl E, Lehmberg J, Steiger HJ, et al. Intraoperative detection of earlymicrovasospasm in patients with subarachnoid hemorrhage by using orthogonalpolarization spectral imaging [J]. Neurosurgery.2003,52(6):1307-1317.
[31]Pennings FA, Bouma GJ, Ince C. Direct observation of the human cerebralmicrocirculation during aneurysm surgery reveals increased arteriolar contractility[J]. Stroke.2004,35(6):1284-1288.
[32]Ohkuma H, Manabe H, Tanaka M, et al. Impact of cerebral microcirculatorychanges on cerebral blood flow during cerebral vasospasm after subarachnoidhemorrhage [J]. Stroke.2000,31(7):1621–1627.
[33]刘承基,编著.脑血管外科学[M].南京:江苏科学技术出版社.1999,10-21.
[34]Rasmussen G, Hauerberg J, Waldemar G, et al. Cerebral blood flow autoregulationin experimental subarachnoid haemorrhage in rat [J]. Acta Neurochir (Wien).1992,119(1-4):128–133
[35]Ebel H, Rust DS, Leschinger A, et al. Vasomotion, regional cerebral blood flow andintracranial pressure after induced subarachnoid haemorrhage in rats [J]. ZentralblNeurochir.1996,57(3):150–155
[36]Yundt KD, Grubb RL Jr, Diringer MN, et al. Autoregulatory vasodilation ofparenchymal vessels is impaired during cerebral vasospasm [J]. J Cereb BloodFlow Metab.1998,18(4):419-424.
[37]Park KW, Metais C, Dai HB, et al. Microvascular endothelial dysfunction and itsmechanism in a rat model of subarachnoid hemorrhage [J]. Anesth Analg.2001,92(4):990-996.
[38]Kozniewska E, Michalik R, Rafalowska J, et al. Mechanisms of vasculardysfunction after subarachnoid hemorrhage [J]. J Physiol Pharmacol.2006,57(suppl11):145-160.
[39]Yamamoto S, Nishizawa S, Tsukada H, et al. Cerebral autoregulation followingsubarachnoid hemorrhage in rats: chronic vasospasm shifts the upper and lowerlimits of the autoregulatory range toward higher blood pressure [J]. Brain Res.1998,782(1-2):194-201.
[40]Asano T, Sano K. Pathogenetic role of no-reflow phenomenon in experimentalsubarachnoid hemorrhage in dogs [J]. J Neurosurg.1977,46(4):454–466.
[41]Sehba FA, Mostafa G, Knopman J, et al. Acute alterations in microvascular basallamina after subarachnoid hemorrhage [J]. J Neurosurg.2004,101(4):633-640.
[42]Sehba FA, Mustafa G, Friedrich V, et al. Acute microvascular platelet aggregationafter subarachnoid hemorrhage [J]. J Neurosurg.2005,102(6):1094-1100.
[43]Naredi S, Lambert G, Eden E, et al. Increased sympathetic nervous activity inpatients with nontraumatic subarachnoid hemorrhage [J]. Stroke.2000,31(4):901-906.
[44]Schwartz AY, Sehba FA, Bederson JB. Decreased nitric oxide availabilitycontributes to acute cerebral ischemia after subarachnoid hemorrhage [J].Neurosurgery.2000,47(1):208-214.
[45]Sehba FA, Schwartz AY, Chereshnev I, et al. Acute decrease in cerebral nitric oxidelevels after subarachnoid hemorrhage [J]. J Cereb Blood Flow Metab.2000,20(3):604-611.
[46]Lambert E, Lambert G, Fassot C, et al. Subarachnoid hemorrhage inducedsympathoexcitation arises due to changes in endothelin and/or nitric oxide activity[J]. Cardiovasc Res.2000,45(4):1046-1053.
[47]Johshita H, Kassell NF, Sasaki T. Blood-brain barrier disturbance followingsubarachnoid haemorrhage in rabbits [J]. Stroke.1990,21(7):1051-1058.
[48]Germano A, d’Avella D, Imperatore C, et al. Time-course of blood brain barrierpermeability changes after experimental subarachnoid hemorrhage [J]. ActaNeurochir (Wien).2000,142(5):575-581.
[49]Imperatore C, Germano A, d'Avella D, et al. Effects of the radical scavanger AVSon behavioral and BBB changes after experimental subarachnoid hemorrhage [J].Life Sci.2000,66(9):779-790.
[50]Sercombe R, Dinh Y R, Gomis P. Cerebrovascular inflammation followingsubarachnoid hemorrhage [J]. Jpn J Pharmacol.2002,88(3):227-249.
[51]Gules I, Satoh M, Nanda A, et al. Apoptosis, blood–brain barrier, andsubarachnoid hemorrhage [J]. Acta Neurochir Suppl.2003,86:483-487.
[52]Cahill J, Calvert JW, Marcantonio S, et al. p53may play an orchestrating role inapoptotic cell death after experimental subarachnoid hemorrhage [J]. Neurosurgery.2007,60(3):531-545.
[53]Park S, Yamaguchi M, Zhou C, et al. Neurovascular protection reduces early braininjury after subarachnoid hemorrhage [J]. Stroke.2004,35(10):2412-2417.
[54]Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injuryafter subarachnoid hemorrhage [J]. Neurol Res.2006,28(4):399-414.
[55]Claassen J, Carhuapoma JR, Kreiter KT, et al. Global cerebral edema aftersubarachnoid hemorrhage: frequency, predictors, and impact on outcome [J]. Stroke.2002,33(5):1225-1232.
[56]Mocco J, Prickett CS, Komotar RJ, et al. Potential mechanisms and clinicalsignificance of global cerebral edema following aneurysmal subarachnoidhemorrhage [J]. Neurosurg Focus.2007,22(5): E7.