摘要
第一部分立体定向建立大鼠C6脑胶质瘤模型
目的:
应用不同数量C6胶质瘤细胞接种大鼠脑内建立大鼠脑胶质瘤模型,观察其生长特性,比较各种接种量的特点。
方法:
分别取1.0×10~5个/10μl,1.0×10~6个/10μl,1.0×10~7个/10μl体外培养的大鼠C6胶质瘤细胞单细胞悬液10μl,立体定向接种于Wistar大鼠脑右侧尾状核区,观察不同接种量实验鼠的生存状态、成瘤情况及脏器转移灶,并采用免疫组织化学方法检测其胶质纤维酸性蛋白、血管内皮生长因子的表达和微血管密度。
结果:
各种接种量的实验组成瘤率均为100%,未见颅外转移病灶,瘤细胞病理性核分裂像多见,胶质纤维酸性蛋白呈散在阳性表达,血管内皮生长因子呈强阳性表达,瘤组织内有出血和坏死以及丰富的微血管,在组织病理学上接近人脑胶质瘤。
结论:
C6细胞立体定向接种Wistar大鼠脑右侧尾状核建立脑深部胶质瘤动物模型,大鼠成瘤率高,颅内生长稳定,肿瘤组织病理学及形态学特性与人脑胶质瘤相似,可作为临床胶质瘤基础研究的理想模型。实验范围内部分时段各种接种剂量肿瘤生长速度差异有显著性意义,可根据病因学、实验治疗或药效学等不同研究需要选择不同接种量。
第二部分C6胶质瘤大鼠放射性脑水肿与CD18mRNA表达的关系
目的:
研究C6胶质瘤大鼠放射性脑损伤后脑水肿的程度以及与血液中性粒细胞CD18mRNA表达水平改变的关系。
方法:
雄性Wistar大鼠40只,体质量250 g -300 g,随机分成A、B两组,每组20只,A组为接受放射线照射组,B组为对照组。两组均颅内种植胶质瘤C6细胞,A组在种植肿瘤细胞15天后予Co60照射,照射后第7天所有实验大鼠均取全脑测含水量;取1mm3大小正常脑组织和肿瘤组织,电镜下观察毛细血管;颈总动脉取血,离心,取中性粒细胞层,逆转录-聚合酶链式反应分析测定血液中性粒细胞CD18mRNA表达水平。
结果:
脑组织含水量:A、B两组间差异有显著性意义(P<0.05);血液中性粒细胞CD18mRNA表达水平:A、B两组间差异有显著性意义(P<0.05)。未接受放射线的胶质瘤组织,电镜下见毛细血管管腔比正常脑组织多见。接受放射线的胶质瘤组织毛细血管受到不同程度的损伤,血管周围水肿。
结论:
放射线可以导致脑水肿的发生,放射性脑水肿的发生与血液中性粒细胞CD18mRNA的改变相关。
第三部分甲基强的松龙及地塞米松治疗放射性脑水肿与CD18mRNA表达的关系
目的:
研究甲基强的松龙与地塞米松对C6胶质瘤大鼠放射性脑损伤后脑水肿程度的影响以及对血液中性粒细胞CD18mRNA表达水平的改变。
方法:
雄性Wistar大鼠100只,体质量250 g -300 g,随机分成5组,每组20只,分别为接受照射同时30mg/kg/d甲基强的松龙治疗组(A组)、接受照射同时10mg/kg/d甲基强的松龙治疗组(B组)、接受照射同时5mg/kg/d地塞米松治疗组(C组)、接受照射但未接受激素治疗的实验对照组(D组)和未接受照射和激素治疗的正常对照组(E组)。各组均颅内种植肿瘤,A、B、C、D四组于种植15天后给予Co60照射,同时所有实验鼠自照射前3天开始静脉注射激素或生理盐水,直至照射后6d,每天1次,照射后第7天取大鼠脑组织测含水量,颈总动脉取血,离心取中性粒细胞层,逆转录-聚合酶链式反应分析测定血液中性粒细胞CD18mRNA表达水平。
结果:
脑组织含水量: D组、E组分别与A、B、C组比较差异均有显著性意义(P<0.05); D、E组两组间比较,差异有显著性意义(P<0.05);C组分别与A、B组比较,差异均有显著性意义(P<0.05);A、B两组间比较,差异无显著性意义(P>0.05)。血液中性粒细胞CD18mRNA表达水平:D、E组分别与A、B、C组比较,差异均有显著性意义(P<0.05);D、E组两组间比较,差异有显著性意义(P<0.05);C组与A、B组比较,差异均有显著性意义(P<0.05);A、B两组间比较,差异无显著性意义(P>0.05)。
结论:
甲基强的松龙与地塞米松均可通过抑制CD18mRNA表达的方式减轻放射性脑水肿,但甲基强的松龙效果较好。
第四部分放射性脑水肿的发生与甲基强的松龙治疗的疗效观察
目的:
研究放射性脑水肿的发病规律和甲基强的松龙与地塞米松治疗放射性脑水肿的效果。
方法:
回顾63例放射性脑水肿患者,统计各种性质占位所占的比例,统计放射线治疗到出现放射性脑水肿症状的时间,比较甲基强的松龙(A组)和地塞米松(B组)治疗放射性脑水肿前后临床症状改变情况和影像学检查脑水肿范围改变情况。
结果:
63例患者中,共有脑膜瘤17例(26.98%),动静脉畸形12例(19.05%),海绵状血管瘤12例(19.05%),脑实质内胶质瘤10例(15.87%),脑室内占位6例(9.52%),垂体腺瘤2例(3.17%),听神经瘤2例(3.17%),松果体区占位1例(1.59%),转移瘤1例(1.59%)。放射性脑水肿症状出现于接受放射线治疗后0月-36月,平均8.1个月,A组治疗有效率92.30%,B组治疗有效率88.89%,其差别没有统计学意义(P>0.05),A组治疗前后脑水肿范围差异有显著性意义(P<0.05),B组治疗前后脑水肿范围差异无显著性意义(P>0.05)。
结论:
窦旁脑膜瘤、海绵状血管瘤、动静脉畸形和胶质瘤等发生放射性脑水肿的危险性较大;放射性脑水肿多发生于患者接受放射线治疗后1年内,尤其是第1个月内和第5个月到第7个月;甲基强的松龙和地塞米松对放射性脑水肿都具有治疗作用,在影像学上,甲基强的松龙效果更好。
PartⅠEstablishment of Rat Cell Line C6 Brain Glioma Model with Stereotaxis
Objective
To establish an brain glioma models of C6 cells in Wistar rats with different methods and to study and compare the growth patterns of the tumors formed in the wistar rat brain.
Methods
Rat C6 glioma cells were cultured in vitro. 10μl of cell suspension containing 1.0×10~5 C6 cells/10μl or 1.0×10~6 C6 cells/10μl or 1.0×10~7 C6 cells/10μl was stereotaxically inoculated into the right caudate nucleus of the rat brain. The moving and survival satates of rats with gliomas were observed. The examinations of the tumors formation, volumes, metastassis and histopathology were performend. The expression of glial fibrillary acidic protein and vascular endothelial growth factor in the tumors and the microvessel density were detected by immunohistochemistry.
Results
All the tested rats of different inoculate dose developed brain tumors without extracranial metastasis. The rat C6 gliomas resembled histopathclogical features of human glioma. The tumors contained many cells with remarkable cytoplasmic and nuclear polymorphism, and pathological mitosis figures. The scattered positive expression of vascular endothelial growth factor was observed in tumor cells. There was the strongly positive expression of glial fibrillary acidic protein in the tumors.
Conclusions
The successful rate of C6 brain tumor model established by the intracerebral inoculation of C6 cells is very high in rats. The tumor established in the experiment is similar to human glioma in histopathological features and it can be used as a good model to study the glioma. The tumors model established by inoculation of different dose of C6 cells can be selected according to different needs of different experiments because their growth speeds are different from each other.
PartⅡThe Relationship Between the Radioactive Cerebral Edema of the Rat of C6 Brain Glioma Model and the Expression of CD18 mRNA
Objective
To study the extent of radioactive cerebral edema and the expression of CD18 of the rat neutrophilic granulocyte.
Methods
40 male Wistar rats were divided into 2 groups at random (n=20). Group A was irradiated with Co60, group B was normal control. Planted glioma cells into brains of rats of group A and B, and treated groups A with Co60 after 15 days. The water content of the brains of the rats and the expression of CD18 of the rats neutrophils were measured 7d after irradiation. Collect the normal brain tissue and the tumor tissue about 1mm3 and observed blood capillary on electron microscope.
Results
The water content of the rats brain: There were significant differences between group A and B (P<0.05).The level of CD18 mRNA: There were significant differences between group A and B (P<0.05). The blood capillary of tumor tissue was much than the normal brain tissue, the blood capillary of tumor tissue of irradiated rat was injuried and have edemata around it.
Conclusion
Radioactive ray can lead to the brain edema and the development of radioactive cerebral edema is related by change of the expression of CD18 in rats.
PartⅢThe Relationship Between the Therapy of Radioactive Cerebral Edema with Methylprednisolone and Dexamethasone and the Expression of CD18 mRNA
Objective
To study the effect of methylprednisolone and dexamethasone to radioactive cerebral edema and the expression of CD18 of the rat neutrophilic granulocyte. Methods
One hundred male Wistar rats were divided into 5 groups atrandom (n=20). Group A was irradiated with 30 mg/kg methylprednisolone, group B was irradiated with 10 mg/kg methylprednisolone, group C was irradiated with 5 mg/kg dexamethasone, group D was irradiated without glucocorticoid, and group E was normal control. Planted glioma cells into brains of rats of group A、B、C、D and E, and treated groups A、B、C、D with Co60 after 15 days. All groups gave glucocorticoid or normal saline beginning 3d before and ending 6d after irradiation(iv, qd), The water content of the brains of the rats and the expression of CD18 of the rats neutrophils were measured 7d after irradiation.
Results
The water content of the rats brain: There were significant differences between group D、E and group A、B、C(P<0.05) , group D and group E(P<0.05), group C and group A、B(P<0.05); There was no significant difference between group A and B(P>0.05). The level of CD18 mRNA: There were significant differences between group D、E and groups A、B、C(P<0.05); group D and group E(P<0.05), group C and group A、B(P<0.05); There was no significant difference between group A and B(P>0.05).
Conclusion
Methylprednisolone and dexamethasone can both protect the radiation-induced injury and brain edema changes by inhibiting the expression of CD18 in rats. and the methylprednisolone is more efficient than dexamethasone.
PartⅣThe Development of Radioactive Cerebral Edema and the Curative Effect of Methylprednisolone
Objective
To study the method of radioactive cerebral edema and the effectiveness of methylprednisolone and dexamethasone.
Methods
63 patients of radioactive cerebral edema were reviewed, the percentage of various kinds entity, the time from radiotherapied to find radioactive cerebral edema were statisticsed. The change of clinical symptom and the ambit of cerebral edema treated with methylprednisolone(group A) or dexamethasone(group B) were compared.
Results
In 63 patients, have 17 meningeoma(26.98%), 12 arteriovenous malformation(19.05%), 12 cavernous angioma(19.05%), 10 glioma(15.87%), 6 tumor in cerebral ventricle(9.52%), 2 hypophyseoma(3.17%), 2 acoustic nerve tumor(3.17%), 1 tumor of apophysis cerebri(1.59%), 1 metastatic tumor(1.59%). 0mon-36mon from radiotherapied, the symptoms of radioactive cerebral edema appeared. Average is 8.1 month. The effective power of group A is 92.30%, The effective power of group B is 88.89%, showing no significant difference. But other than in group B, significant differences of ambit of cerebral edema between pretherapy and post-treatment were detected in group A(P<0.05).
Conclusions
Parasagittal sinus meningioms, arteriovenous malformation, cavernous angioma, glioma and tumor in cerebral ventricle have more chance of radioactive cerebral edema. Radioactive cerebral edema often betide 1 year after radiotherapiy, especially in 1st month and 5~(th) mon-7~(th) mon. Methylprednisolone and dexamethasone can both protect the radiation-induced injury. And the methylprednisolone is more efficient than dexamethasone in imageology.
引文
1 Merienne L, Laurenl A, Meder JF, et al. Slereolaxic irradiation of 46 cerebral angiomas. Analysis of the angiographic results 2 and a half years after treatment[J] .Neurochirurgie,1991,37(3):185-195.
2郑国梁,曾其祥,吴沛宏,等.鼻咽癌放疗后放射性脑病的CT分析.中华放射学杂志,1990,24(6):367-370.
3 Crossen JR, Garwood D, Glatstein E. Neurobehavioral seguelae ofcranial irradiation in adults. Clin Oncol, 1994.12(3):627-642.
4王如,王守森.放射外科迟发性反应的有关问题.中国微侵袭神经外科杂志,1998,3(3): 222-224.
5刘延鹏,李玲,王志刚,等.脑转移瘤X刀治疗后瘤周脑水肿的转归,山东大学学报(医学版),2005,43(6):548-549.
6 Rabinstein AA. Treatment of cerebral edema. Neurologist. 2006,12(2):59-73.
7彭家仪,马志忠.脑水肿的诊断与治疗(第一版).北京:人民军医出版社,1996. 38.
8 Adams RD. The neuropathology of radiosurgery. Stereotect Funt Neurosurg, 1991, 57; 82.
9 Ostertage CB Stereotactic radiation therapy and radiosurgery. Stereotact Funt Neurosury, 1994, 63: 220.
10 Wu H, Prince JE, Brayton CF, et al. Hostresistance of CD18 knockout mice against systemic infection with Listeria monocytogenes. InfectImmun, 2003, 71(10):5986-5993.
11 Clatterbuck RE, Gailloud P, OgataL , et al. Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates. J Neurosurg, 2003, 99(2):376-382
12 Arnould BT, Michiels C, Remacle J, et al. Hypoxic Human Umbilical Vein Endothelial Cells Induce Activation of Adherent Polymorphonuclear Leukocytes. Blood,1994,83:3705-3716.
13 Wallis WJ, Beatty PG, Ochs HD, et al. Human Monocyte Adherence to Cultured Vascular Endothelium: Monoclonal Antibody-Defined Mechanisms. J Immunology, 1985,135(4):2323-2330.
14 Pober JS, Bevilacqua MP, Menerick DL, et al. Two Distinct Monolanes, Interleukin 1 and Tumor Necrosis Factor, Each Independently Induce Biosynthesis and Transient Expression of the Same Surface of Cultured Human Vascular Endothelial Cells. J Immunol, 1986, 136(5):1680-1687.
15 Van de Stolpe A, Van der Saag PT. Intercellular Adhesion Molecule-1. J.Mol.Med 1996,74:13-33.
16倪海洋,杨雪辉.细胞粘附分子CD11b/ CD18与糖尿病血管病变.浙江临床医学,200,4(12) :956-957.
17 Bevilacqua MP, Nelson RM, Mannori G, et al. Endothelial-leukocyte adhesion molecules in human disease. Annu Rev Med, 1994; 45(2):361-378.
18 Rhee P, Morris J, Durham R, et al. Recombinant humanized monoclonal antibody against CD18(rhuMAb CD18) in traumatic hemorrhagic shock: results of a phaseⅡclinical trial[J]. Trauma discussion, 2000,49(4): 611-619.
19 Love S, Barber R. Expression of Pselectin and intercellular adhesion molecule in human brain after focal infarction or cardiac arrest[J]. Neuropathol Appl Neurobiol, 2001,27(6): 465-473.
20 Tajra LC, Martin X, Margonari J, et al. Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not major renal ischaemic injury[J]. Nephrol Dial Transplant, 2000,15(10):1556-1561.
21 Chang JH, Chang JW, Choi JY, et al. Complications after gamma knife radiosurgery for benign meningiomas[J]. J Neurol Neurosurg Psychiatry, 2003,74(2):226-230.
22 Singh VP, Kansai S, Vaishya S, et al. Early complications following gamma knife radiosurgery for intracranial meningiomas[J]. J Neurosurg, 2000,93(Suppl 3):57-61.
23 Braughler JM, Hall ED. et al. Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester. J Neurosurg. 1983,58(4):538-42.
24叶钦勇,郑安.甲基强的松龙冲击疗法治疗放射性脑病的临床研究.中国神经免疫学和神经病学杂志, 2003,10(4):251-254.
25杨军,秋楠,许彦钢,等. X-刀治疗脑部病变后并发脑水肿与病变种类关系的探讨.中国微侵袭神经外科杂志, 2000, 5(3):153-155.
1 Weiss WA, Burns MJ, Hackett C, et al. Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res, 2003,63(7):1589-1595
2 Ckicoine MR, Silbergeld DL. Invading C6 glioma cells maintaining tumorigenicitv. J Veurosurg, 1995,83(7):665.
3 Peterson DL, Sheridan PJ, Brown WE. Animal models for brain tumors: historical perspectives and future directions [J]. J Neurosurg, 1994; 80(5):865-876.
4 Kobavashi N, Allen N, Clendenon NR, et al. An improved rat brain tumor model. J Neurosurg, 1980, 53( 9):808.
5林松,吴建中,王忠诚,等.人类野生型p53基因对9L胶质肉瘤的抑制作用.中华神经外科杂志,1997,13(4):215.
6幸兵,任祖渊,苏长保.一种新的大鼠脑胶质瘤动物模型的建立.中国医学科学院学报,1998,20(4):241.
7 Wilson CB, Norrell HJ, Barker M. Intrathecal injection of methotrexate (NSC-740) in transplanted brain tumors [J]. Cancer Chemother Rep, 1967,51(1):1-6.
8 Benda P, Lightbody J, Sato G, et al. Differentiated rat glial cell strain in tissue culture. Science, 1968; 161(839): 370-371.
9 Morreale VM, Herman BH, Der-Minassian V, et al. A brain-tumor model utilizing stereotactic implantation of a permanent cannula. J Neurosurg, 1993,78(6): 959-965.
10 Kobayashi N, Allen N, Clendenon NR, et al. An improved brain-tumor model. J Neurosurg, 1980; 53(6): 808-815.
11 Benda P, Someda K, Messer J, et al. Morphological and immunochemical studies of rat glial tumors and clonal strains propagated in culture [J]. J Neurosurg, 1971,34(3):311-323.
12 Schmidek HH, Nielsen SL, Schiller AL, et al. Morphological studies of rat brain tumors induced by N-nitosomethylurea [J]. J Neurosurg, 1971,34(3):335-340.
13 Schubert D, Heinemann S, Carlisle W, et al. Clonal cell lines from the rat central nervous system [J]. Nature, 1974,249(454):224-227.
14 Sergey E, Dave Q, Carlos R, et al. Brain tumor development in rats is associated with changes in central nervous system cytokine and neuropeptide systems. J Brain Research, 1999, 4: 363-373.
15 DE Ridder L. Behaviour of gliomas in vitro vs histopathological grading. Tnt J Devl Neuroscience, 1999, 17:541-546.
16赵世光,张建华,姜宝红,等. C6脑胶质瘤动物模型肿瘤细胞的超微结构观察.电子显微学报,2000, 19:23-27.
17焦保华.脑立体定向建立C6大鼠脑胶质瘤模型.河北医科大学学报,2000,21(4):208-210.
18吴景文,章翔,高大宽,等,建立大鼠C6脑胶质瘤模型与观察颅内肿瘤生长.第四军医大学学报,2000,21(3):307-310.
19张云亭,刘松龄,杨学军,等.自杀基因治疗鼠C6脑胶质瘤模型的动态MRI研究.临床放射学杂志,1999,18(1):53-56.
20王伟民,朱诚,张光雾,等.脑立体定向接种C6细胞建立大鼠脑胶质瘤模型.中华实验外科杂志,1995, 12(4):221-222.
21李维方,张光霁,朱诚,等.VEGF反义寡核苷酸抑制荷瘤大鼠胶质瘤血管生成的作用和效果.解放军医学杂志,2003,28(2):144-145.
22 Watanabe K, Sakamoto M, somiya M, et al. Feasibility and limitations of the rat model by C6 gliomas implanted at the subcutaneous region. Neurol Res, 2002 Jul; 24(5):485-490.
23 Zhang Y ,Wang Y, Zhang Y, et al. C6 glioma cells retrovirally engineered to express IL-18 and Fas exert FasL-dependent cytotoxicity against glioma formation. Biochem Biophys Res Commun,2004,325(4):1240-1245.
24 Li Y, Owusu A, Lehnert S. Treatment of intracranial rat glioma model with implant of radiosensitizer and biomodulator drug combined with external beam radiotherapy. Int J Radiat Oncol Biol Phys, 2004,58(2):519-527.
25高大宽,章翔,吴景文,等.建立大鼠C6脑胶质瘤模型的有效方法.中华实验外科杂志,2000,17(1):93-95.
26 Utermark T, Schubert SJ, Hanemann CO. Rearrangements of the intermediate filament GFAP in primary human schwannoma cells[J].Veurobiol Dis, 2005, 19(12):1-9.
27 Bikfalvi A. Recent developments in the inhibition of angiogenesis: examples from studies on platelet factor 4 and the VFGF/ VFGF R system[J]. Biochem Pharmacol, 2004, 68(6):1017-1721.
28孙慧勤,邹仲敏,卜修武,等.生长因子在脑胶质瘤血管生成及其恶性进展中的作用[J].国外医学(生理、病理科学与临床分册),2000, 20(6):50l-504.
29 Vince GH, Bendszus M, Schweitzer, et al. Spontaneous regression of experimental gliom as-an immunoh is tochemical and MRI study of the C6 glioma spheroid implantation model. J Experimental Neurology, 2004,190:478-485.
1郑国梁,曾其祥,吴沛宏,等.鼻咽癌放疗后放射性脑病的CT分析.中华放射学杂志,1990,24(6):367-370.
2 Crossen JR, Garwood D, Glatstein E. Neurobehavioral seguelae ofcranial irradiation in adults. Clin Oncol, 1994.12(3):627-642.
3王如,王守森.放射外科迟发性反应的有关问题.中国微侵袭神经外科杂志,1998,3(3):222-224.
4刘延鹏,李玲,王志刚,等.脑转移瘤X刀治疗后瘤周脑水肿的转归,山东大学学报(医学版),2005,43(6):548-549.
5王来兴,何晓文,周晓平.地塞米松对放射性脑水肿大鼠中性粒细胞CD18表达的抑制用.第二军医大学学报,2004,25(9):970-973.
6罗超,刘运生,赵贤军,等.伤灶局部引流和亚低温联合治疗创伤性脑损伤的实验研究.医学临床研究,2005,22(5):643-646.
7杨军,秋楠,许彦钢,等. X-刀治疗脑部病变后并发脑水肿与病变种类关系的探讨.中国微侵袭神经外科杂志,2000, 5(3):153-155.
8冯军,赵洪洋,胡雪芝等.立体定向建立大鼠C6脑胶质瘤模型.中华实验外科杂志,2006,23(11):1416.
9 MerienneL, LaurentA, Meder JF, et al. Stereotaxic irradiation of 46 cerebral angiomas. Analysis of the angiographic results 2 and a half years after treatment. [J] Neurochirurgie, 1991, 37(3):185-195.
10胡小吾,周晓平,王来兴,等.脑部疾病X刀治疗后症状性放射性脑水肿分析[J].临床神经外科学杂志,2001,3:101-102.
11 Liscak R, Vladyka V, Novotny J, et al. Leksell gamma knife lesioning of the rat hippocampus: the relationship between radiation dose andfunctional and structural damage[J]. Neurosurgery, 2002,97:666-673.
12 Liu Y, Xiao S, Liu M, et al. Analysis of related factors in complications of stereotactic radiosurgery in intracranial tumors[J]. Stereotact Funct Neurosurg, 2000, 75(2-3):129-132.
13 Kroppenstedt SN, Thomale UW, Griebenow M, et al. Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygena-tion, and edema formation in brain-injured rats[J]. Crit Care Med, 2003, 31(8):2211-2221.
14 MacGregor DG, Avshalumov MV, Rice ME. Brainedema induced by in vitro ischemia: causal factors and neuroprotection[J]. J Neurochem, 2003, 85(6):1402-1411.
15 Schulthesis TE,Kun LE,Ang KK,et al. Radiation response of the central nervous system[J]. Int J Radiat Oncol Biol Phys,1995,31:1093-1097.
16 Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol. 2004, 16(6): 593-600.
17彭家仪,马志忠.脑水肿的诊断与治疗(第一版).北京:人民军医出版社,1996. 38.
18 Levin VA,Edwards MS, Byrd A. Quantitative observation of theacute. effects of X-irradiation of brain capillary permeability. Int J Radiat Oncol Biol Phys, 1979,5(7):1627-1631.
19 Rubin P ,Gash DM,Hansen JT,et al.Disruption of the bloob brain barrier as the primaryeffect of CNS irradiation. Radiother Oncol, 1994,31:51.
20倪海洋,杨雪辉.细胞粘附分子CD11b/ CD18与糖尿病血管病变.浙江临床医学,2002, (12) :956-957.
21 Bevilacqua MP, Nelson RM, Mannori G, et al. Endothelial-leukocyte adhesion molecules in human disease. Annu Rev Med, 1994; 45(2):361-378.
22 Rainger GE, Buckley C, Simmons DL, et al. Cross-talk between cell adhesion molecules regulates the migration velocity of neutrophils. Curr Biol ,1997 ,7 :316-325.
23 Wu H, Prince JE, Brayton CF, et al. Hostresistance of CD18 knockout mice against systemic infection with Listeria monocytogenes. InfectImmun, 2003, 71(10):5986-5993.
24 Clatterbuck RE, Gailloud P, OgataL , et al. Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates. J Neurosurg, 2003, 99(2):376-382.
25 Bauer TR, Hickstein DD. Genetherapy for leukocyte adhesion deficiency[J]. Curr Opin Mol Ther, 2000,2(4):383-388.
26卢建,余应年,徐仁宝.主编:受体信号转导系统与疾病(第一版).济南:山东科技出版社。1999:304-328.
27王忠诚.主编:神经外科学(第一版).武汉:湖北科学技术出版社,2002:55.
28 Rhee P, Morris J, Durham R, et al. Recombinant humanized monoclonal antibody against CD18(rhuMAb CD18) in traumatic hemorrhagic shock: results of a phaseⅡclinical trial[J]. Trauma discussion, 2000,49(4): 611-619.
29 Love S, Barber R. Expression of Pselectin and intercellular adhesion molecule in human brain after focal infarction or cardiac arrest[J]. Neuropathol Appl Neurobiol, 2001,27(6): 465-473.
30 Tajra LC, Martin X, Margonari J, et al. Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not major renal ischaemic injury[J]. Nephrol Dial Transplant, 2000,15(10):1556-1561.
31 El Shehaby A, Ganz JC, Reda WA,et al. Mechanisms of edema after gamma knife surgery for meningiomas. Report of two cases. J Neurosurg. 2005, 102:1-3.
1 Rabinstein AA. Treatment of cerebral edema. Neurologist. 2006,12(2):59-73.
2 Chang JH, Chang JW, Choi JY, et al. Complications after gamma knife radiosurgery for benign meningiomas[J]. J Neurol Neurosurg Psychiatry, 2003,74(2):226-230.
3 Singh VP, Kansai S, Vaishya S, et al. Early complications following gamma knife radiosurgery for intracranial meningiomas[J]. J Neurosurg, 2000,93(Suppl 3):57-61.
4叶钦勇,郑安.甲基强的松龙冲击疗法治疗放射性脑病的临床研究.中国神经免疫学和神经病学杂志,2003,10(4):251-254.
5王来兴,何晓文,周晓平.地塞米松对放射性脑水肿大鼠中性粒细胞CD18表达的抑制用.第二军医大学学报,2004,25(9):970-973.
6罗超,刘运生,赵贤军,等.伤灶局部引流和亚低温联合治疗创伤性脑损伤的实验研究.医学临床研究,2005,22(5):643-646.
7王嗣欣,周丽红,李艳,等.大剂量甲基强的松龙对缺血再灌注大鼠脑组织兴奋性氨基酸的影响.承德医学院学报,2001,18:99-102. 8赵丽云,龚玉华,于建设,等.心肺复苏后大剂量GC对脑单胺类神经递质及脑组织结构的影响.中华麻醉学杂志. 2004, 24 (5):352-356.
9 Hzmmerschmidt DE, White JG, Graddock PR, et al. Corticosteroids inhibit complement - induced granulocyte aggregation∶A possible mech2 anismfor their efficacy in shock states1. J Clin Invest , 1979 , 63:798-893.
10 Braughler JM,Hall ED, Means ED,et al.Evaluation of an intensive methylprednisolone sodium succinate dosing regimen in experimental spinalcord injury. J Neurosurg, 1987,67(1):102-105
11 Bracken MB, ShepardMJ, Collins WF, et al. A randomized, controlled of methylprednisolone or naloxone in the treatment of acute spinalcord injury. New England J Medicine, 1990, 332(20):1405.
12 Giannotta SL,Weiss MH, Apuzzo MT, et al. High dose glucocorticoids in the management of severe head injury. Neurosurg, 1984; 15(4):497.
13 Hall ED. The neuroprotective pharmacology of methylprednisolone. J Neurosurg, 1992,76(1):13.
14 Bracken MB, Shepard MJ, Collins WF, et al. Methylprednisolone or naloxone treatment after acute spinal cord injury. 1-year follow-up data. J Neurosurg, 1992, 76(1):23.
15 Braughler JM, Hall ED, Means ED, et al. Evaluation of an intensive methylprednisolone sodium succinate dosing regimen in experimental spinal cord injury. Veurosurg, 1987, 67(2):102.
16 Mursch K, Buhre W, Behnke-Mursch J, et al. Peroperative cardiovascular stability during brain stem surgery. The use of high-dose methylprednisolone compared to dexamethasone. A retrospective analysis. ActaAnaest hesiol Scand, 2000, 44(4):378-382
17 Ishimitsu H, Matsumoto A, Takemoto M, et al. Effect of various kinds of glucocorticoids on experimental brain edema (author's transl), No Shinkei Geka. 1980 Oct, 8(10):951-957.
18 Zhu C, Zhang GJ , Yang ZJ , et al. An evaluation of the effect of largedose of dexamethasone on postoperative brain edema inpatientswith severe head injury J. Chin J Trauma, 1997 ,13 (1):1-5.
19 Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol. 2004,16(6): 593-600.
20 Shirane R, Niizuma H, Suzuki J. A study of the optimum dose of a glucocorticoid, methylprednisolone sodium succinate, before and after neurosurgical major operations--relationship between beta-glucuronidase level and post operative brain edema. No To Shinkei. 1985, 37(9):913-917.
21 Lyons RP, Necoman PK, Saunders M. Methylprednisone therapy in multiple sclerosis: clinical adverse effects. J Neurol Neurosurg Psychiatry, 1998, 51(2):285.
22 Durelli L, Cocito D, Ricco A, et al. High-dose intravenous methylprednisolone in the treatment of multiplesclerosis: clinical-immunologic correlations. Neurology, 1986, 36(2):238
23 El Shehaby A, Ganz JC, Reda WA, et al. Mechanisms of edema after gamma knife surgery for meningiomas. Report of two cases. J Neurosurg. 2005, 102:1-3.
24 Kozler P, Pokorny J. Effects of intracarotid injection of methylprednisolone on cellular oedema after osmotic opening of the blood-brain barrier in rats. Prague Med Rep.2004;105(3):279-290.
25 Sinha S, Bastin ME, Wardlaw JM, Armitage PA, Whittle IR. Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study. Neurol Neurosurg Psychiatry. 2004 Nov,75(11):1632-1635.
26 Bastin ME, Carpenter TK, Armitage PA, et al. Effects of dexamethasone on cerebral perfusion and water diffusion in patients with high-grade glioma. AJNR Am J Neuroradiol. 2006 Feb,27(2):402-408.
27江基尧,朱诚,罗其中,主编:颅脑创伤临床救治指南(修订版,第二版).上海:第二军医大学出版社,2003,81-83.
28 Andersen C, Astrup J, Gyldensted C. Quantitative MR analysis of glucocorticoid effects on peritumoral edema associated with intracranial meningiomas and metastases. J Comput Assist Tomogr. 1994 Jul-Aug, 18(4):509-518.
1 Buatti JM, Friedman WA, Theele DP, et al. The lazaroid U74389Gprotects normal brain from stereotactic radiosurgery-induced radiation injury. Int J Radiat Oncol Biol Phys, 1996,34:591.
2 Kalapurakal JA, Silverman CL, Akhtar N, et al. Intracranial meningiomas: factors that influence the development of cerebral edema after stereotactic radiosurgery and radiationtherapy. Radiology, 1997,204(2):461-465.
3 Fike JR, CannCE, TurowskiK, et al. Radiation dose response of normal brain[J]. Int J Radiat Oncol BiolPhys, 1988,14(1):63-70.
4 Bitzer M, Topka H, Morgalla M, et al. Tumor-related venous obstruction and development of peritumora brain edema in meningioma[J]. Neurosurgery, 1998, 42(4):730-737.
4 Ganz JC, Schrouner O,Pendl G. Radiation-induced edema after Gamma Knife treatmenet for meningiomas. Stereotact Funct Neurosurg. 1996,66 :1129-1133.
5 Chang JH, Chang JW, Choi JY, et al. Complications after gamma knife radiosurgery for benign meningiomas. J Newrol Neurosurg Psychiatry, 2003,74(2):226-230.
6符江,滕良珠,丁峰,等.脑膜瘤VEGF表达与瘤周脑水肿及相关因素的关系:山东大学学报(医学版)2003, 41(2):135-138.
7张方成,朱贤立,汪占春等.脑膜瘤Γ-刀治疗后长期脑水肿1例,同济医科大学学报,1997,26 (6):491.
8 Flickinger JC, Kondziolka D, Kalend AM, et al. Radiosurgery-related imaging changes in surrounding brain: multivariate analysis and model evaluation. In:Kondziolka D ed. Radiosurgery, Vol 1, Karger: Basel, 1996:229-236.
9 Shenouda G, Souhami L, Podgorsak EB, et al. Radiosurgery and accelerated radiotherapy for patients with glioblastoma. Can J Neurol Sci, 1997,24(2):110.
10 Flickinger JC, Kondziolka D, Pollock BE, et al. Complications from arteriovenous malformation radiosurgery: multivariate analysis and risk modeling. Int J Radiat Oncol BiolPhys, 1997,38(3):485.
11杨军,秋楠,许彦钢,等. X-刀治疗脑部病变后并发脑水肿与病变种类关系的探讨.中国微侵袭神经外科杂志. 2000, 5(3):153-155.
12 Adams RD. The neuropathology of radiosurgery. Stereotect Funt Neurosurg, 1991, 57:82.
13 Ostertage CB. Stereotactic radiation therapy and radiosurgery. Stereotact Funt Neurosury,1994, 63:220.
1 Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol. 2004; 16(6): 593-600.
2 Rabinstein AA. Treatment of cerebral edema. Neurologist. 2006;12(2):59-73
3杨利孙,章翔,易声禹,等.下丘脑局部兴奋与创伤性脑水肿发生关系的研究J .解放军医学杂志,2001,26(8):564-566.
4徐如祥,齐一龙,张新伟,等.酚妥拉明、心得安治疗创伤性脑水肿的实验研究J .安徽医学,2000 ,21(2):21-24.
5许川.创伤性脑水肿的发生机制及治疗研究进展.创伤外科杂志, 2004, 6(5):381-384.
6 Book AA, Ranganathan S, Abounader R, et al. Scatter factor/hepatocyte growth factor gene transfer increases rat blood-glioma a barrier perm eability[J]. Brain Res, 1999,833(2):173-180.
7 Monsky WL, Fukumura D, Gohongi T, et al. Augmentation of transvascular growth factor [J]. CancerRes, 1999,59(16):4129-4135.
8 Bertossi M, Virgintino D, Maiorano E, et al. Ultrastructural and morphometric investigation of human brain capillaries in normal and peritumoral tissues [J].Ultrastruct Pathol, 1997, 21(1):41-49.
9范乐明.脑水肿发病机理研究的某些进展[J] .江苏医药,1986,6(10):543-545.
10于明琨,朱诚,张光霁,等.急性脑损伤后猫突触膜N-甲基-D-天门冬氨酸受体的变化[J].中华神经外科杂志, 1995,11(6):347.
11 Torer RD, Conollv RB. An investigation of the role of Microsomal oxidative metabolism in the in vivo genntoxicitv of 1, 2-dihaloethanes[J]. Toxicol Appl Pharmaeol, 1985,77:36-46.
12徐如祥,易声禹,吴声伶,等.神经细胞Ca2+通道变化及对鼠血脑屏障通透性和外伤性脑水肿的影响J .中华神经外科杂志,1992,8(1):41.
13 Anonymous. Molecular mechanism of brain injury and edema J. Acta Neurochir, 2000,76(5):27-28.
14徐如祥.创伤性脑水肿研究进展.中国现代神经疾病杂志. 2004,4(3):141-145.
15 Boulard G. Plasma osmolarity and cerebral volume[J]. Ann Fr Anesth Reanim, 2001,20(2):196-202
16罗成义,徐如祥,王清华,等.大鼠皮质N-甲基-D-天冬氨酸受体在脑损伤后的时相变化[J],中国病理生理杂志,1999,15(5):450-452.
17罗成义,徐如祥.脑损伤后谷氨酸含量变化与脑水肿的关系[J].广东医学, 1999,20(2):88-89.
18尹飞,杨于嘉,虞佩兰,等.大鼠脑水肿脑组织谷氨酸与γ-氨基丁酸的改变及黄芩甙对其影响[J].中国中西医结合杂志,200020(7):524-526.
19 Schulatz K, Ghosh L, Banerje ES. Neoplastic expression in murine cells induced by halogenated hydrocarbons[J]. Vitro Cell Dev Bio1, 1992,28A(4):267-272.
20 Qiu LX, Shi SH, Xing SB, et al. Rate constants for the reactions of OH with five halogenated substituted ethanes from 292K to 366K[J].J Phys Chem, 1992,96:685-689.
21 Ide M, Jimbo M, Kubo O, et al. Peritumoral brain edema and cortical damage by meningioma[J]. Acta Neurochir Suppl (Wien), 1994, 60:369-372.
22陆兵勋.脑水肿的治疗研究进展.解放军保健医学杂志,2006,(8)1:48-53.
23 Oken DE. Renal and extrarenal considerations in high dose mannitol theraphy. RenFail, 1994,16(1):147.
24李强,陆兵勋.脑水肿的治疗研究进展.实用医药杂志2005, (22)1:79-81.
25 Ware ML, Nemani VM , MeekerM , et al. Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery, 2005,57(4):727-736.
26 Vialet R, Albanese J, Thomachot L, et al. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension:2mL/kg 7.5% saline is more effective than 2 ml/kg 20% mannitol. Crit Care Med, 2003, 31(6):1683-1687.
27 Munar F, Ferrer AM, de Nadal M, et al. Cerebral hemodynamic effects of 7. 2%hypertonic saline in patients with head injury and raised intracranial pressure. J Neurotrauma, 2000,17(1):41-51.
28 Kaal EC, Vecht CJ. The management of brain edema in brain tumors. Curr Opin Oncol. 2004,16(6):593-600.
29 MurschK, BuhreW, Behnke-MurschJ, et al. Peroperative cardiovascular stability during brain stem surgery. The use of high-dose methylprednisolone compared to dexamethasone. A retrospective analysis.ActaAnaest hesiol Scand, 2000, 44(4):378-382.
30 Ishimitsu H, Matsumoto A, Takemoto M, et al. Effect of various kinds of glucocorticoids on experimental brain edema (author's transl), No Shinkei Geka. 1980 Oct,8(10):951-957.
31 Zhu C, Zhang GJ , Yang ZJ , et al. An evaluation of the effect of largedose of dexamethasone on postoperative brain edema inpatientswith severe head injury J. Chin J Trauma, 1997,13(1):1-5.
32 Shirane R, Niizuma H, Suzuki J. A study of the optimum dose of a glucocorticoid, methylprednisolone sodium succinate, before and after neurosurgical major operations-relationship between beta-glucuronidase level and post operative brain edema. No To Shinkei. 1985,37(9):913-917.
33 Lyons RP, Necoman PK, Saunders M. Methylprednisone therapy in multiple sclerosis: clinical adverse effects. J Neurol Neurosurg Psychiatry, 1998, 51(2):285.
34 Durelli L, Cocito D, Ricco A, et al. High-dose intravenous methylprednisolone in the treatment of multiplesclerosis: clinical-immunologic correlations. Neurology, 1986, 36(2):238.
35 Kaal EC, Vecht CJ, Curr Opin Oncol. The management of brain edema in brain tumors. 2004; 16(6): 593-600.
36 Asakura K, Matsuo Y, Kanemasa T, et al. P/Q-type Ca2+ channel blocker omega-agatoxin IVA protects against brain injury after focal ischemia in rats. Brain Res, 1997.776(1-2):140-145.
37 Gordon E. Post-traumatic and postoperative treatment of severe brain injuries with controlled hyperventilation. Acta Anaesthesiol Belg. 1976, 27, suppl:291-297.
38 Rishi Gupta E, Sander Connolly, Stephan Mayer, et al. Hemicraniectomy for MassiveMiddle Cerebral Artery Territory Infarction A Systematic Review. Stroke, 2004, 35:539-543.
39 Huang Z, Huang PL, Panahian N, er al. Effects of cerebral ischemia in mice defficient in neuronal nitric oxide synthase. Science, 1994, 265(5180):1883.
40 Yasuma Y, Strasser A, Ruetzel C. et al. The effect of nitric oxide inhibition on ischemic brain edema. Aeta Neurocir Suppl(Wien), 1997,70:202.