新生儿缺氧缺血性脑病血清NSE、NBNA评分及临床表现相关性研究
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摘要
研究背景
新生儿缺氧缺血性脑病(HIE)是指围产期窒息导致脑的缺氧缺血性损害,是我国新生儿急性死亡和慢性神经系统后遗症的重要原因之一,其早发现、早诊断、早干预对降低我国新生儿围生期死亡率及致残率,提高人口质量有很大意义。
由于缺血缺氧性脑损伤可导致神经细胞的坏死崩解,细胞浆及细胞器内一些特异的分子释放(如S-100,NSE等),检测这些分子的存在,为HIE的诊断提供了途径。其中神经元特异性烯醇化酶(NSE)是特定存在于神经元细胞和神经内分泌细胞内的一种酶,当上述神经细胞由于缺氧缺血发生死亡,该酶可从细胞内释放出来,脑脊液以及外周血中该酶浓度的升高可作为神经细胞损伤的标志,具有很高灵敏性和一定特异性。
新生儿20项行为神经评定(NBNA评分),是我国学者在总结国外新生儿行为神经功能评定方法的基础上,发展的一套适合在我国开展并已得以广泛应用的神经行为评估方法,对新生儿缺氧缺血性脑病患儿病情及预后的评估和预计有显著意义。
目的
本研究旨在探讨新生儿缺氧缺血性脑病中血清神经元特异性烯醇化酶(neuron-specific enolase,NSE)及新生儿20项行为神经评定(Neonatal BehaviralNeurological Assessment,NBNA)的变化、二者与HIE的临床表现分度的关系,以及二者之间的相关性,为HIE早期诊断和病情评估提供依据。
方法
选取50例新生儿为研究对象,其中HIE患儿40例为实验组,足月儿按国内统一的标准进行诊断和临床表现分度,早产儿中有明确围生期缺氧缺血病史,生后有典型神经系统异常表现者诊断为HIE,并参照国内相关文献进行临床分度;同期分娩的非HIE新生儿10例做为对照组。研究对象均选择合适的时间采血查血清NSE值,并进行NBNA评分。排除可引起NSE升高的其他疾病。用统计分析的方法,分别比较两组中足月儿和早产儿各自不同临床表现组的血清NSE值变化和NBNA评分的差异,观察上述两项指标是否与HIE的临床分度一致,各临床分度间上述两项指标各自差异是否显著。并研究血清NSE值与NBNA评分的相关性。
结果
随着临床表现程度的加重,足月儿血清NSE值呈现逐渐增高,而NBNA评分逐渐降低。NSE值、NBNA评分在对照组与各实验组之间差异明显(P＜0.05);随着临床表现程度的加重,早产儿血清NSE值也呈现逐渐增高,而NBNA评分逐渐降低。中、重度组HIE早产儿NSE值、NBNA评分之间、及各自较对照组差异显著(P＜0.05),但轻度HIE组患儿NSE值、NBNA评分较对照组差异不明显(P＞0.05)。此外,早产儿血清NSE值与NBNA评分之间有较好的相关性(r=-0.72576),可建立回归方程:Y=888.66615-22.18736X(X为NBNA评分值,Y为NSE监测值)。
结论
血清NSE值及NBNA评分均是反映HIE及其神经功能损伤的敏感指标,且与临床表现分度基本一致。两指标之间也存在一定相关性,临床可通过对两指标的测定对HIE进行早期诊断与评估。
Background
Neonatal hypoxic ischemic encephalopathy(HIE) refers to the hypoxic and ischemic brain injury after perinatal asphyxia,which plays an important role in neonatal acute death and chronic sequelae in our country.It is of great significance to give early detection,diagnosis and intervention in degrading the mortality and disability rate of the perinatal stage and elevating the population quality.
Because of the necrosis and disaggregation of the neurocyte,some special molecules(such as S-100,NSE,et al) are released by the cytoplasm and organelle.It provides an effective way for HIE diagnosis to detect the existence of these molecules. Neuron-specific enolase(NSE) is an enzyme that specialized located in the neuron cells and the neural endocrine cells.The enzyme can be released from these cells after their death induced by hypoxic ischemic injury.It is a sign of neurocytic injury that the concentration of this enzyme evaluating in cerebrospinal fluid and peripheral circulation, with high sensitivity and certain specificity.
Neonatal Behaviral Neurological Assessment(NBNA) is a system of behaviral neurological assessment that develops from foreign behaviral neurological assessments and it is suitable for widely practicing in our country.It is also of great significance to undertake behaviral neurological assessment in evaluating the condition and the prognosis of the neonates.
Purpose
To investigate the variance of the serum neuron-specific enolase(NSE) level and the Neonatal Behaviral Neurological Assessment(NBNA) score of the HIE neonates,and the relation between the clinical graduation and the both above,which may provide the evidence for evaluation and early diagnosis of the disease.
Methods
50 neonates are brought into the research,including 10 normal ones for control group and 40 HIE ones for experimental group,in which term neonates are diagnosed and graduated by domestic unified standards,and preterm ones are diagnosed by their precise hypoxic and ischemic history.All the research objects are obtained blood samples for NSE detecting and proceeded NBNA on proper time,expelled other interference diseases.Statistics analysis is used to determine the differences of NSE levels and NBNA scores between each group.Full term neonates and pre-term ones are compared individually.The concordance between the index above and clinical graduating and the dependablity between the HIE levels and NBNA scores are also determined.
Results
In full term neonates,as the aggravation of the degree of HIE,the serum NSE levels get increased and NBNA scores get decreased.There are significant differences of NSE levels and NBNA scores between the control group and experimental group(P＜0.05). There are also significant differences of NSE levels and NBNA scores between each degree of the experimental group(P＜0.05).It indicates that in preterm neonates,as the aggravation of the clinical manifestation degree,the serum NSE levels get increased and the NBNA scores get decreased.Compared with the control group,the NSE levels and NBNA scores of the moderate and the severe HIE group have significant differences and there are also significant differences between the two groups(P＜0.05).However,the differences of the two indexes between the mild HIE group and the control group is not significant(P＞0.05).In preterm neonates,serum NSE levels have good dependability with NBNA scores(r=-0.72576):Y=888.66615-22.18736 X(X=NBNA score,Y=NSE level)
Conclusion
Serum NSE level and NBNA score are sensitive index of HIE and its neurological injury.And they are concordance with the clinical manifestation degrees.There are correlations between the two indexes.We can perform early diagnosis and evaluation of HIE by utilization of the two indexes.
新生儿缺氧缺血性脑病(HIE)是指围产期窒息导致脑的缺氧缺血性损害,是我国新生儿急性死亡和慢性神经系统后遗症的重要原因之一,其早发现、早诊断、早干预对降低我国新生儿围生期死亡率及致残率,提高人口质量有很大意义。
由于缺血缺氧性脑损伤可导致神经细胞的坏死崩解,细胞浆及细胞器内一些特异的分子释放(如S-100,NSE等),检测这些分子的存在,为HIE的诊断提供了途径。其中神经元特异性烯醇化酶(NSE)是特定存在于神经元细胞和神经内分泌细胞内的一种酶,当上述神经细胞由于缺氧缺血发生死亡,该酶可从细胞内释放出来,脑脊液以及外周血中该酶浓度的升高可作为神经细胞损伤的标志,具有很高灵敏性和一定特异性。
新生儿20项行为神经评定(NBNA评分),是我国学者在总结国外新生儿行为神经功能评定方法的基础上,发展的一套适合在我国开展并已得以广泛应用的神经行为评估方法,对新生儿缺氧缺血性脑病患儿病情及预后的评估和预计有显著意义。
目的
本研究旨在探讨新生儿缺氧缺血性脑病中血清神经元特异性烯醇化酶(neuron-specific enolase,NSE)及新生儿20项行为神经评定(Neonatal BehaviralNeurological Assessment,NBNA)的变化、二者与HIE的临床表现分度的关系,以及二者之间的相关性,为HIE早期诊断和病情评估提供依据。
方法
选取50例新生儿为研究对象,其中HIE患儿40例为实验组,足月儿按国内统一的标准进行诊断和临床表现分度,早产儿中有明确围生期缺氧缺血病史,生后有典型神经系统异常表现者诊断为HIE,并参照国内相关文献进行临床分度;同期分娩的非HIE新生儿10例做为对照组。研究对象均选择合适的时间采血查血清NSE值,并进行NBNA评分。排除可引起NSE升高的其他疾病。用统计分析的方法,分别比较两组中足月儿和早产儿各自不同临床表现组的血清NSE值变化和NBNA评分的差异,观察上述两项指标是否与HIE的临床分度一致,各临床分度间上述两项指标各自差异是否显著。并研究血清NSE值与NBNA评分的相关性。
结果
随着临床表现程度的加重,足月儿血清NSE值呈现逐渐增高,而NBNA评分逐渐降低。NSE值、NBNA评分在对照组与各实验组之间差异明显(P＜0.05);随着临床表现程度的加重,早产儿血清NSE值也呈现逐渐增高,而NBNA评分逐渐降低。中、重度组HIE早产儿NSE值、NBNA评分之间、及各自较对照组差异显著(P＜0.05),但轻度HIE组患儿NSE值、NBNA评分较对照组差异不明显(P＞0.05)。此外,早产儿血清NSE值与NBNA评分之间有较好的相关性(r=-0.72576),可建立回归方程:Y=888.66615-22.18736X(X为NBNA评分值,Y为NSE监测值)。
结论
血清NSE值及NBNA评分均是反映HIE及其神经功能损伤的敏感指标,且与临床表现分度基本一致。两指标之间也存在一定相关性,临床可通过对两指标的测定对HIE进行早期诊断与评估。
Background
Neonatal hypoxic ischemic encephalopathy(HIE) refers to the hypoxic and ischemic brain injury after perinatal asphyxia,which plays an important role in neonatal acute death and chronic sequelae in our country.It is of great significance to give early detection,diagnosis and intervention in degrading the mortality and disability rate of the perinatal stage and elevating the population quality.
Because of the necrosis and disaggregation of the neurocyte,some special molecules(such as S-100,NSE,et al) are released by the cytoplasm and organelle.It provides an effective way for HIE diagnosis to detect the existence of these molecules. Neuron-specific enolase(NSE) is an enzyme that specialized located in the neuron cells and the neural endocrine cells.The enzyme can be released from these cells after their death induced by hypoxic ischemic injury.It is a sign of neurocytic injury that the concentration of this enzyme evaluating in cerebrospinal fluid and peripheral circulation, with high sensitivity and certain specificity.
Neonatal Behaviral Neurological Assessment(NBNA) is a system of behaviral neurological assessment that develops from foreign behaviral neurological assessments and it is suitable for widely practicing in our country.It is also of great significance to undertake behaviral neurological assessment in evaluating the condition and the prognosis of the neonates.
Purpose
To investigate the variance of the serum neuron-specific enolase(NSE) level and the Neonatal Behaviral Neurological Assessment(NBNA) score of the HIE neonates,and the relation between the clinical graduation and the both above,which may provide the evidence for evaluation and early diagnosis of the disease.
Methods
50 neonates are brought into the research,including 10 normal ones for control group and 40 HIE ones for experimental group,in which term neonates are diagnosed and graduated by domestic unified standards,and preterm ones are diagnosed by their precise hypoxic and ischemic history.All the research objects are obtained blood samples for NSE detecting and proceeded NBNA on proper time,expelled other interference diseases.Statistics analysis is used to determine the differences of NSE levels and NBNA scores between each group.Full term neonates and pre-term ones are compared individually.The concordance between the index above and clinical graduating and the dependablity between the HIE levels and NBNA scores are also determined.
Results
In full term neonates,as the aggravation of the degree of HIE,the serum NSE levels get increased and NBNA scores get decreased.There are significant differences of NSE levels and NBNA scores between the control group and experimental group(P＜0.05). There are also significant differences of NSE levels and NBNA scores between each degree of the experimental group(P＜0.05).It indicates that in preterm neonates,as the aggravation of the clinical manifestation degree,the serum NSE levels get increased and the NBNA scores get decreased.Compared with the control group,the NSE levels and NBNA scores of the moderate and the severe HIE group have significant differences and there are also significant differences between the two groups(P＜0.05).However,the differences of the two indexes between the mild HIE group and the control group is not significant(P＞0.05).In preterm neonates,serum NSE levels have good dependability with NBNA scores(r=-0.72576):Y=888.66615-22.18736 X(X=NBNA score,Y=NSE level)
Conclusion
Serum NSE level and NBNA score are sensitive index of HIE and its neurological injury.And they are concordance with the clinical manifestation degrees.There are correlations between the two indexes.We can perform early diagnosis and evaluation of HIE by utilization of the two indexes.
引文
[1]中华医学会儿科分会新生儿组.新生儿缺氧缺血性脑病诊断标准[J].中华儿科杂志,2005,43(8):584.
[2]Celtik C,Acunas B,Oner N.Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J].Brain &Development,2004,26(6):398-402.
[3]新生儿行为神经协作组.应用20项新生儿行为神经测定预测窒息儿的预后[J].中华儿科杂志,1994,32(4):210-212.
[4]陈惠金.早产儿缺氧缺血性脑病诊断标准探讨[J].临床儿科杂志,2004,22(11):712-713,716.
[5]陈绪文,虞人杰.早产儿缺氧缺血性脑病的诊断和治疗[J].中华儿科杂志,2004,42(12):940-941
[6]Vannucci RC,Perlman JM.Interventions for perinatal hypoxic-ischemic encephalopathy[J].Pediatrics 1997,100(6):1004-1014.
[7]鲍秀兰.新生儿行为和0～3岁教育[M].北京:中国少年儿童出版社,1995:120.
[8]Hatfield RH,McKernan RM.CSF neuron-specific enolase as a quantitative marker of neuronal damage in a rat stroke model[J].Brain Res,1992,577(2):249-252
[9]Kecskes Z,Dunster KR,Colditz PB.NSE and S100 after hypoxia in the newborn pig[J]._Pediatr Res,2005,58(5):953-7.
[10]Daval JL,Pourie G,Grojean S.Neonatal hypoxia triggers transient apoptosis followed by neurogenesis in the rat CA1 hippocampus[J].Pediatr Res,2004,55(4):561-567.
[11]Thornberg E,Thiringer K,Hagberg H.Neuron specific enolase in asphyxiated newborns:association with encephalopathy and cerebral function monitor trace[J].Arch Dis Child Fetal Neonatal Ed,1995,72(1):F39-42.
[12]Barone FC,Clark RK,Price WJ,et al.Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia[J].Brain Res,1993,623(1):77-82.
[13]Akman I,Ozek E,Kulekci S,et.Auditory neuropathy in hyperbilirubinemia:is there a correlation between serum bilirubin,neuron,specific enolase levels and auditory neuropathy?[J].Int J Audiol,2004,43(9):516-522.
[14]Celtik C,Acunas B,Oner N,et al.Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J].Brain Dev,2004,26(6):398-402.
[15]Berger R,Richichi R.Derivation and validation of an equation for adjustment of neuron-specific enolase concentrations in hemolyzed serum[J].Pediatr Crit Care Med,2009,10(2):260-3.
[16]Dean JM,Gunn A J,Wassink G,et al.Endogenous alpha2-adrenergic receptor-mediated neuroprotection after severe hypoxia in preterm fetal sheep[J].Neuroscience,2006,142(3):615-628.
[17]黄燕萍,李小权等.神经元特异性烯醇酶在早期评估新生儿缺氧缺血性脑病预后中的价值[J].新生儿科杂志,2005,20(1):23-26.
[18]薛辛东,杜立中.儿科学[M].北京:人民卫生出版社,2005:120-121.
[1]中华医学会儿科分会新生儿组.新生儿缺氧缺血性脑病诊断标准[J].中华儿科杂志,2005,43(8):584.
[2]薛辛东,杜立中.儿科学[M].北京:人民卫生出版社,2005:120-121.
[3]陈惠金.早产儿缺氧缺血性脑病诊断标准探讨[J].临床儿科杂志,2004,22(11):712-713,716.
[4]陈绪文,虞人杰.早产儿缺氧缺血性脑病的诊断和治疗[J].中华儿科杂志,2004.42(12):940-941.
[5]Celtik C,Acunas B,Oner N.Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J].Brain &Development,2004,26(6):398-402.
[6]鲍秀兰.新生儿行为和0～3岁教育[M].北京:中国少年儿童出版社,1995:120.
[7]新生儿行为神经协作组.应用20项新生儿行为神经测定预测窒息儿的预后[J].中华儿科杂志,1994,32(4):210-212.
[8]Iives P,Lintrop M,Metsvaht T.Cerebral blood flow velocities in predicting outcome of asphyxiated newborn infants[J].Acta Paediatr,2004,93(4):523-528.
[9]Somjen GG,Aitken PG,Czeh G,et al.Cellular physiology of hypoxia of the mammalian central nervous system.In Waxman SG eds.Molecular and Cellular approaches to the treatment of neurological disease[M].New York:Raven Press,1993,316-324.
[10]Young RS,Petroff OA,Aquila WJ,et al.Hyperglycemia and the rate of lactic acid accumulation during cerebral ischemia in developing animals:in vivo proton MRS study[J].Biol Neonate,1992;61(4):235-42.
[11]Miyabe M,Kirsch JR,Nishikawa Y,et al.Comparative analysis of brain protection by N-methyl-D-aspartate receptor antagonists after transient focal ischemia in cats[J].Crit Care Med,1997 Jun;25(6):1037-1043.
[12]王小引,王凯,李平法.缺氧缺血性脑病大鼠脑内兴奋性氨基酸含量动态变化[J].实用儿科临床杂志,2002,17(1):36-37.
[13]Hallebeck JM,et al.Background review and current concepts of reperfusion injury.Arch Neurol 1990;47:1245-1253.
[14]Nelson CW,et al.Oxygen radicals in cerebral ischemia.Am J Physiol 1992;263:H1356-H1362.
[15]韩玉昆,许植之,虞人杰.新生儿缺氧缺血性脑病[M].北京:人民卫生出版社,2000:38.
[16]Kristian-T,Siesjo-BK.Calcium in ischemic cell death.Stroke,1998;29(3):705-718.
[17]蒙来成.新生儿窒息血钙浓度与多器官损害关系的探讨(附164例分析).新生儿科杂志,1994,9(4):156-158.
[18]Vannucci RC,Brucklacher RM,Vannucci SJ.Intracellular calcium accumulation during the evolution of hypoxic-ischemic brain damage in the immature rat[J].Brain Res Dev Brain Res,2001,126(1):117-120.
[19]Huguet F,Guerraoui-A,Barrie L,et al.Changes in excitatory amino acid levels and tissue energy metabolites of neonate rat brain after hypoxia and hypoxia-ischemia[J].Neurosci Lett,1998;240(2):102-106.
[20]Emerson MR,Nelson SR,Samson FE,et al.Hypoxia preconditioning attenuates brain edema associated with kainic acidi-induced status epilepticus in rats[J].Brain Res,1999,825(1-2):183-93.
[21]C.Chiesa,G.Pellegrini,A.Panero,et al.Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia[J].Eur J Clin Invest,2003,33(4):352-358.
[22]Wang J,Lu Q.Expression of T subsets and mIL-2R in peripheral blood of newborns with hypoxic ischemic encephalopathy[J].World J Pediatr,2008,4(2):140-4.
[23]Touzani O,Boutin H.Potential mechanisms of interleukin-1 involvement in cerebral ischaemia[J].J Neuroimmunol,1999,100(1-2):203-215.
[24]Fabian RH,Perez-Polo JR,Kent TA.Electrochemical monitoring of superoxide anion production and cerebral blood flow:effect of interleukin-1 beta pretreatment in a model of focal ischemia and reperfusion [J]. J Neurosci Res, 2000, 60(6):795-803.
[25] YANG G.-Y.,YING MAO,ZHOU L.-F. Expression of intercellular adhesion molecule 1 (ICAM-1) is reduced in permanent focal cerebral ischemic mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist[J]. Brain Res Mol Brain Res, 1999 ,65(2): 143-50.
[26] Girard S, Larouche A, Kadhim H,et al. Lipopolysaccharide and hypoxia /ischemia induced IL-2 expression by microglia in neonatal brain[J]. Neuroreport , 2008,19(10):997-1002.
[27] Aly H, Khashaba MT, El-Ayouty M, et al. IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy[J]. Brain Dev, 2006, 28(3):178-82.
[28] Nikolaos Kostulas, Sigliti Henrietta Pelidou, Pia Kivisakk, et al. Increased IL-1β, IL-8, and IL-17 mRNA Expression in Blood Mononuclear Cells Observed in a Prospective Ischemic Stroke Study[J].Strock, 1999, 30(10):2147-2179.
[29] Ramaswamy V, Horton J, Vandermeer B. Systematic review of biomarkers of brain injury in term neonatal encephalopathy[J]. Pediatr Neurol, 2009, 40(3):215-226.
[30] Bartha AI, Foster-Barber A, Miller SP,et al. Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome[J]. Pediatr Res, 2004, 56(6):960-966.
[31] Mesples B, Plaisant F, Gressens P. Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice [J]. Brain Res Dev Brain Res, 2003, 141(1-2):25-32.
[32] Markus T, Hansson S, Amer-Wahlin I. Cerebral inflammatory response after fetal asphyxia and hyperoxic resuscitation in newborn sheep[J]. Pediatr Res, 2007,62(1):71-7.
[33] Schwab JM, Nguyen TD. Human focal cerebral infarctions induce differential lesional interleukin-16 (IL-16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and activated microglia/macrophages [J]. J Neuroimmunol, 2001, 114(1-2):232-241.
[34] Li GZ, Zhong D, Yang LM. Expression of interleukin-17 in ischemic brain tissue [J]. Scand J Immunol, 2005, 62(5):481-6.
[35] Hedtjarn M, Mallard C, Arvidsson P,et al. White matter injury in the immature brain: role of interleukin-18[J].Neurosci Lett, 2005, 373(1):16-20.
[36] Lavine SD, Hofman FM, Zlokovic BV. Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury[J]. J Cereb Blood Flow Metab, 1998 , 18(1):52-8.
[38] Szaflarskin J, Burtum K, Silverstein FS. Cerebral hypoxic-ischemia stimulates cytokine gene expression in perinatal rats [J]. Stroke, 1995, 26(6): 1093-1100.
[39] Dhandapani KM, Brann DW. Transforming growth factor-beta: a neuroprotective factor in cerebral ischemia[J]. Cell Biochem Biophys, 2003 , 39(1):13-22.
[40] Buisson A, Lesne S, Docagne F. Transforming growth factor-beta and ischemic brain injury[J]. Cell Mol Neurobiol, 2003, 23(4-5):539-50.
[41] Wrana JL.,Attisano L, Wieser Rotraud. Mechanism of activation of the TGF-β receptor. Nature, 1994, 370(4):341-347.
[42]Clawson, T.F., Vannucci, S.J.,Wang, G.M.,et al. Hypoxia-ischemia-induced apoptotic cell death correlates with IGF-I mRNA decrease in neonatal rat brain [J]. Biol Signals Recept, 1999 , 8(4-5):281-93.
[43] Beilharz EJ, Russo VC, Butler G. Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury[J]. Brain Res Mol Brain Res, .1998 , 59(2):119-34.
[44] Yamaguchi F, Itano T, Miyamoto O. Increase of extracellular insulin-like growth factor I (IGF-I) concentration following electrolytical lesion in rat hippocampus [J]. Neurosci Lett, 1991, 128(2):273-6.
[45] Beilharz EJ, Williams CE, Dragunow M. Mechanisms of delayed cell death following hypoxic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss[J]. Brain Res Mol Brain Res, 1995, 29(1):1-14.
[46] Pons S, Torres-Aleman I. Basic fibroblast growth factor modulates insulin-like growth factor-I, its receptor, and its binding proteins in hypothalamic cell cultures [J]. Endocrinology,1992,131(5):2271-8.
[47]Lee WH,Bondy C.Insulin-like growth factors and cerebral ischemia[J].Ann N Y Acad Sci,1993,679:418-22.
[48]Guan J,Bennet L,Gluckman PD.Insulin-like growth factor-1 and post-ischemic brain injury[J].Prog Neurobiol,2003,70(6):443-462.
[49]Tagami M,Yamagata K,Nara Y.Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats[J].Lab Invest,1997,76(5):603-612.
[50]Guan J,Bennet TL,George S.Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep[J].Neuroscience,2000,95(3):831-9.
[51]Tamm I,Kikuchi T.Insulin-like growth factor-1(IGF-1),insulin,and epidermal growth factor(EGF) are survival factors for density-inhibited,quiescent Balb/c-3T3murine fibroblasts[J].J Cell Physiol,1990,143(3):494-500.
[52]D'Mello SR,Borodezt K,Soltoff SR Insulin-like growth factor and potassium depolarization maintain neuronal survival by distinct pathways:possible involvement of PI 3-kinase in IGF-1 signaling[J].J Neurosci,1997,17(5):1548-1560.
[53]Parrizas M,LeRoith D.Insulin-like growth factor-1 inhibition of apoptosis is associated with increased expression of the bcl-xL gene product[J].Endocrinology,1997,138(3):1355-1358.
[54]Nicholas RS,Stevens S,Wing MG.Microglia-derived IGF-2 prevents TNFalpha induced death of mature oligodendrocytes in vitro[J].J Neuroimmunol,2002,124(1-2):36-44.
[55]Guan J,Williams CE,Skinner SJ.The effects of insulin-like growth factor (IGF)-1,IGF-2,and des-IGF-1 on neuronal loss after hypoxic-ischemic brain injury in adult rats:evidence for a role for IGF binding proteins[J].Endocrinology,1996,137(3):893-8.
[56]Cowell RM,Plane JM,Silverstein FS.Complement activation contributes to hypoxic-ischemic brain injury in neonatal rats[J].J Neurosci,2003,23(28):9459-9468.
[57]Devlin LA,Nguyen MD,Figueroa E,et al.Effects of endotoxin administration and cerebral hypoxia-ischemia on complement activity and local transcriptional regulation in neonatal rats[J] Neurosci Lett, 2005, 390(2): 109-113.
[58] Ten VS, Sosunov SA, Mazer SP,et al. C1q-deficiency is neuroprotective against hypoxic-ischemic brain injury in neonatal mice[J]. Stroke, 2005 , 36(10):2244-50.
[59] Grether JK, Nelson KB, Dambrosia JM,et al. Interferons and cerebral palsy. J Pediatr, 1999,134(3):324-32.
[60] Sonntag J, Wagner MH, Strauss E,et al. Complement and contact activation in term neonates after fetal acidosis[J]. Arch Dis Child Fetal Neonatal Ed, 1998 , 78(2):F125-8.
[61] Zhang ZG, Chopp M. Zaloga C, et al. Cerebral endothelial nitric oxide synthase expression after fotal cerebral ischemia in rats[J] . Stroke , 1993 , 24(12):2016-2021 .
[62] AmerF, Samdani, Ted M, Dawson, et,al. Nitric oxide synthase in models of focal ischemia[J]. Stroke, 1997, 28(6): 1283-1288.
[63] Nagayama M, Zhang F, Iadecola C. Delayed treatment with aminoguanidine decreases focal cerebral ischemic damage and enhances neurologic recovery in rats[J]. J Cereb Blood Flow Metab, 1998, 18(10): 1107-1113.
[64] Choi DW. Nitric Oxide: Foe Of friend to the injured brain[J]. ProcNatlAcad Sci U S A, 1993, 90(21):9741-9743.
[65] Iadecola C, Zhang F, Xu S,et al. Inducible nitric oxide synthase gene expression in brain following cerebral ischemia[J]. J Cereb Blood Flow Metab, 1995, 15(3):378-84.
[66] Beasley TC, Bari F, Thore C,et al. Cerebral ischemia/reperfusion increases endothelial nitric oxide synthase levels by an indomethacin-sensitive mechanism [J]. J Cereb Blood Flow Metab, 1998, 18(1):88-96.
[67] Liesz A, Suri-Payer E, Veltkamp C,et al. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke [J]. Nat Med, 2009, 15(2): 192-9.
[68]Brittis PA, Flanagan JG. Nogo domains and a Nogo receptor: implicationsfor axon regeneration[J]. Neuron, 2001, 30(1): 11-4.
[69] Fenghua HU, Betty P, Stephane B, et al. Nogo-A interacts with the Nogo-66 receptor through multiple sites to create an isoform -selective subnanornolar agonist[J]. J Neurosci, 2005, 25(22): 5298-5304.
[70] Jin WL, Liu YY, Liu HL, el al. Intraneuronal localization of Nogo-A in the rat. [J]. J Comp Neurol, 2003, 458(1):1-10.
[71] Josephson A, Trifunovski A, Scheele C,et al. Activity-induced and developmental downregulation of the Nogo receptor[J]. Cell Tissue Res, 2003, 311(3):333-42.
[72] Oertle, T., Schwab, M. E., et al.Nogo and its partners[J]. TrendsCell Biol.,2003, 13(4):187-194.
[73] Li, Q., Qi, B., Oka, K., Shimakage,M. et al. Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer[J]. Oncogene 2001, 20(30), 3929-3936.
[74] Meier S, Brauer AU, Heimrich B,et al. Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure[J]. FASEB J., 2003 , 17(9): 1153-5.
[75] Huber AB, Weinmann O, Brosamle C,et al. Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions [J]. J Neurosci, 2002 , 22(9):3553-3567.
[76] Kim JE, Bonilla IE, Qiu D,et al. Nogo-C is sufficient to delay nerve regeneration[J]. Mol Cell Neurosci. 2003, 23(3):451-459.
[77] Schachner M, Bartsch U. Multiple functions of the myelin-associated glycoprotein MAG (siglec-4a) in formation and maintenance of myelin. [J], Glia, 2000, 29(2): 154-165.
[78] Mukhopadhyay G, Dohe～y P, Walsh FS, et al . A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron, 1994, 13(3):757-767.
[79] Wang KC, Koprivica V, Kim JA,et al. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth[J]. Nature , 2002 , 417(6892):941-944.
[80] Jean WC, Spellman SR, Nussbaum ES, et al. Reperfusion injury after focal cerebral ischemia : the role of inflammation and the therapeutic horizon [J]. Neurosurgery, 1998, 43(6): 1382-1396.
[81] Nurden AT, Bihour C, Macchi L, et al. Platelet activation in thrombotic disorders[J]. NouvRev FrHematol, 1993, 35(1): 67-71.
[82] Turowski P, Adamson P, Greenwood J. Pharmacological targeting of ICAM-1 signaling in brain endothelial cells: potential for treating neuroinflammation[J]. 2005, 25(1): 153-170.
[83] Krupinski J, Kaluza J, Kumar P,et al. Role of angiogenesis in patient with cerebral ischemic stroke.Stroke, 1994, 25(9):1794-1798.
[84] Lau D, Mollnau H, Eiserich JP, et al. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc Natl Acad Sci U S A, 2005, 102(2):431-436.
[85] Vestweber D, Blanks JE. Mechanisms that regulate the function of the selectins and their ligands[J]. Physiol Rev, 1999, 79(1): 181-213.
[86] Cherian P, Hankey GJ, Eikelboom JW,et al. Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes[J]. Stroke, 2003, 34(9):2132-2137.
[87] Milner R, Campbell IL. The extracellular matrix and cytokines regulate microglial integrin expression and activation[J]. J Immunol, 2003, 170(7):3850-3858.
[88] Mousa SA.av vitronectin receptors in vascular-mediated disorders[J]. Medicinal Res Rev, 2003, 23(2): 190-199.
[89] Celtik C, Acunas. B, Oner N,et al. Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J]. Brain Dev, 2004, 26(6):398-402.
[90] Lima JE, Takayanagui OM, Garcia LV. Use of Neuron-specific enolase for assessing the severity and outcome in patients with neurological disorders[J]. Braz J Med Biol Res, 2004, 37(1): 19-26.
[91] Csrcia-Alix, Cabanas F, Pellicer A, et al. Neuron-specific enolase and myelin basic protein: Relationship of cerebrospinal fluid condition of asphyxiated full-term infants[J].Pediatrics,1994,93(2):234-240.
[92]Nagdyman N,K(o|¨)men W,Ko HK,M(u|¨)ller C,Obladen M.Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia[J].Pediatr Res,2001,49(4):502-506.
[93]Vannucci RC,Perlman JM.Interventions for perinatal hypoxic-ischemic encephalopathy[J].Pediatrics,1997,100(6):1004-1014.
[94]Lorek A,Takei Y,Cady EB,Wyatt JS,Penrice J,Edwards AD,et al.Delayed (secondary) cerebral energy failure after acute hypoxiaischemia in the newborn piglet:continuous 48-h studies by phosphorus magnetic resonance spectroscopy[J].Pediatr Res,1994,36(6):699-706.
[95]Barone FC,Clark RK,Price WJ,et al.Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia[J].Brain Res,1993,623(1):77-82.
[96]Thoresen M.Cooling the newborn after asphyxia-physiological and experimental background and its clinical use[J].Semin Neonatol,2000,5(1):61-73.
[97]Verdu Perez A,Falero MP,Arroyos A,et al.Blood neuronal specific enolase in newborns with perinatal asphyxia[J].Rev Neurol,2001,32(8):714-717.
[98]邓辉,唐从海等.NBNA评分对新生儿缺氧缺血性脑病预后评估应用的临床意义[J].实用医技杂志,2008,15(18):2405-2406.
[99]黄燕萍,李小权等.神经元特异性烯醇酶在早期评估新生儿缺氧缺血性脑病预后中的价值[J].新生儿科杂志,2005,20(1):23-26.
[100]晁占湖,王有福等.NBNA评分筛查足月高危儿脑损伤及早期干预的临床应用[J].中国实用神经疾病杂志,2008,11(1):84-87.
[2]Celtik C,Acunas B,Oner N.Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J].Brain &Development,2004,26(6):398-402.
[3]新生儿行为神经协作组.应用20项新生儿行为神经测定预测窒息儿的预后[J].中华儿科杂志,1994,32(4):210-212.
[4]陈惠金.早产儿缺氧缺血性脑病诊断标准探讨[J].临床儿科杂志,2004,22(11):712-713,716.
[5]陈绪文,虞人杰.早产儿缺氧缺血性脑病的诊断和治疗[J].中华儿科杂志,2004,42(12):940-941
[6]Vannucci RC,Perlman JM.Interventions for perinatal hypoxic-ischemic encephalopathy[J].Pediatrics 1997,100(6):1004-1014.
[7]鲍秀兰.新生儿行为和0～3岁教育[M].北京:中国少年儿童出版社,1995:120.
[8]Hatfield RH,McKernan RM.CSF neuron-specific enolase as a quantitative marker of neuronal damage in a rat stroke model[J].Brain Res,1992,577(2):249-252
[9]Kecskes Z,Dunster KR,Colditz PB.NSE and S100 after hypoxia in the newborn pig[J]._Pediatr Res,2005,58(5):953-7.
[10]Daval JL,Pourie G,Grojean S.Neonatal hypoxia triggers transient apoptosis followed by neurogenesis in the rat CA1 hippocampus[J].Pediatr Res,2004,55(4):561-567.
[11]Thornberg E,Thiringer K,Hagberg H.Neuron specific enolase in asphyxiated newborns:association with encephalopathy and cerebral function monitor trace[J].Arch Dis Child Fetal Neonatal Ed,1995,72(1):F39-42.
[12]Barone FC,Clark RK,Price WJ,et al.Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia[J].Brain Res,1993,623(1):77-82.
[13]Akman I,Ozek E,Kulekci S,et.Auditory neuropathy in hyperbilirubinemia:is there a correlation between serum bilirubin,neuron,specific enolase levels and auditory neuropathy?[J].Int J Audiol,2004,43(9):516-522.
[14]Celtik C,Acunas B,Oner N,et al.Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J].Brain Dev,2004,26(6):398-402.
[15]Berger R,Richichi R.Derivation and validation of an equation for adjustment of neuron-specific enolase concentrations in hemolyzed serum[J].Pediatr Crit Care Med,2009,10(2):260-3.
[16]Dean JM,Gunn A J,Wassink G,et al.Endogenous alpha2-adrenergic receptor-mediated neuroprotection after severe hypoxia in preterm fetal sheep[J].Neuroscience,2006,142(3):615-628.
[17]黄燕萍,李小权等.神经元特异性烯醇酶在早期评估新生儿缺氧缺血性脑病预后中的价值[J].新生儿科杂志,2005,20(1):23-26.
[18]薛辛东,杜立中.儿科学[M].北京:人民卫生出版社,2005:120-121.
[1]中华医学会儿科分会新生儿组.新生儿缺氧缺血性脑病诊断标准[J].中华儿科杂志,2005,43(8):584.
[2]薛辛东,杜立中.儿科学[M].北京:人民卫生出版社,2005:120-121.
[3]陈惠金.早产儿缺氧缺血性脑病诊断标准探讨[J].临床儿科杂志,2004,22(11):712-713,716.
[4]陈绪文,虞人杰.早产儿缺氧缺血性脑病的诊断和治疗[J].中华儿科杂志,2004.42(12):940-941.
[5]Celtik C,Acunas B,Oner N.Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J].Brain &Development,2004,26(6):398-402.
[6]鲍秀兰.新生儿行为和0～3岁教育[M].北京:中国少年儿童出版社,1995:120.
[7]新生儿行为神经协作组.应用20项新生儿行为神经测定预测窒息儿的预后[J].中华儿科杂志,1994,32(4):210-212.
[8]Iives P,Lintrop M,Metsvaht T.Cerebral blood flow velocities in predicting outcome of asphyxiated newborn infants[J].Acta Paediatr,2004,93(4):523-528.
[9]Somjen GG,Aitken PG,Czeh G,et al.Cellular physiology of hypoxia of the mammalian central nervous system.In Waxman SG eds.Molecular and Cellular approaches to the treatment of neurological disease[M].New York:Raven Press,1993,316-324.
[10]Young RS,Petroff OA,Aquila WJ,et al.Hyperglycemia and the rate of lactic acid accumulation during cerebral ischemia in developing animals:in vivo proton MRS study[J].Biol Neonate,1992;61(4):235-42.
[11]Miyabe M,Kirsch JR,Nishikawa Y,et al.Comparative analysis of brain protection by N-methyl-D-aspartate receptor antagonists after transient focal ischemia in cats[J].Crit Care Med,1997 Jun;25(6):1037-1043.
[12]王小引,王凯,李平法.缺氧缺血性脑病大鼠脑内兴奋性氨基酸含量动态变化[J].实用儿科临床杂志,2002,17(1):36-37.
[13]Hallebeck JM,et al.Background review and current concepts of reperfusion injury.Arch Neurol 1990;47:1245-1253.
[14]Nelson CW,et al.Oxygen radicals in cerebral ischemia.Am J Physiol 1992;263:H1356-H1362.
[15]韩玉昆,许植之,虞人杰.新生儿缺氧缺血性脑病[M].北京:人民卫生出版社,2000:38.
[16]Kristian-T,Siesjo-BK.Calcium in ischemic cell death.Stroke,1998;29(3):705-718.
[17]蒙来成.新生儿窒息血钙浓度与多器官损害关系的探讨(附164例分析).新生儿科杂志,1994,9(4):156-158.
[18]Vannucci RC,Brucklacher RM,Vannucci SJ.Intracellular calcium accumulation during the evolution of hypoxic-ischemic brain damage in the immature rat[J].Brain Res Dev Brain Res,2001,126(1):117-120.
[19]Huguet F,Guerraoui-A,Barrie L,et al.Changes in excitatory amino acid levels and tissue energy metabolites of neonate rat brain after hypoxia and hypoxia-ischemia[J].Neurosci Lett,1998;240(2):102-106.
[20]Emerson MR,Nelson SR,Samson FE,et al.Hypoxia preconditioning attenuates brain edema associated with kainic acidi-induced status epilepticus in rats[J].Brain Res,1999,825(1-2):183-93.
[21]C.Chiesa,G.Pellegrini,A.Panero,et al.Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia[J].Eur J Clin Invest,2003,33(4):352-358.
[22]Wang J,Lu Q.Expression of T subsets and mIL-2R in peripheral blood of newborns with hypoxic ischemic encephalopathy[J].World J Pediatr,2008,4(2):140-4.
[23]Touzani O,Boutin H.Potential mechanisms of interleukin-1 involvement in cerebral ischaemia[J].J Neuroimmunol,1999,100(1-2):203-215.
[24]Fabian RH,Perez-Polo JR,Kent TA.Electrochemical monitoring of superoxide anion production and cerebral blood flow:effect of interleukin-1 beta pretreatment in a model of focal ischemia and reperfusion [J]. J Neurosci Res, 2000, 60(6):795-803.
[25] YANG G.-Y.,YING MAO,ZHOU L.-F. Expression of intercellular adhesion molecule 1 (ICAM-1) is reduced in permanent focal cerebral ischemic mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist[J]. Brain Res Mol Brain Res, 1999 ,65(2): 143-50.
[26] Girard S, Larouche A, Kadhim H,et al. Lipopolysaccharide and hypoxia /ischemia induced IL-2 expression by microglia in neonatal brain[J]. Neuroreport , 2008,19(10):997-1002.
[27] Aly H, Khashaba MT, El-Ayouty M, et al. IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy[J]. Brain Dev, 2006, 28(3):178-82.
[28] Nikolaos Kostulas, Sigliti Henrietta Pelidou, Pia Kivisakk, et al. Increased IL-1β, IL-8, and IL-17 mRNA Expression in Blood Mononuclear Cells Observed in a Prospective Ischemic Stroke Study[J].Strock, 1999, 30(10):2147-2179.
[29] Ramaswamy V, Horton J, Vandermeer B. Systematic review of biomarkers of brain injury in term neonatal encephalopathy[J]. Pediatr Neurol, 2009, 40(3):215-226.
[30] Bartha AI, Foster-Barber A, Miller SP,et al. Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome[J]. Pediatr Res, 2004, 56(6):960-966.
[31] Mesples B, Plaisant F, Gressens P. Effects of interleukin-10 on neonatal excitotoxic brain lesions in mice [J]. Brain Res Dev Brain Res, 2003, 141(1-2):25-32.
[32] Markus T, Hansson S, Amer-Wahlin I. Cerebral inflammatory response after fetal asphyxia and hyperoxic resuscitation in newborn sheep[J]. Pediatr Res, 2007,62(1):71-7.
[33] Schwab JM, Nguyen TD. Human focal cerebral infarctions induce differential lesional interleukin-16 (IL-16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and activated microglia/macrophages [J]. J Neuroimmunol, 2001, 114(1-2):232-241.
[34] Li GZ, Zhong D, Yang LM. Expression of interleukin-17 in ischemic brain tissue [J]. Scand J Immunol, 2005, 62(5):481-6.
[35] Hedtjarn M, Mallard C, Arvidsson P,et al. White matter injury in the immature brain: role of interleukin-18[J].Neurosci Lett, 2005, 373(1):16-20.
[36] Lavine SD, Hofman FM, Zlokovic BV. Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury[J]. J Cereb Blood Flow Metab, 1998 , 18(1):52-8.
[38] Szaflarskin J, Burtum K, Silverstein FS. Cerebral hypoxic-ischemia stimulates cytokine gene expression in perinatal rats [J]. Stroke, 1995, 26(6): 1093-1100.
[39] Dhandapani KM, Brann DW. Transforming growth factor-beta: a neuroprotective factor in cerebral ischemia[J]. Cell Biochem Biophys, 2003 , 39(1):13-22.
[40] Buisson A, Lesne S, Docagne F. Transforming growth factor-beta and ischemic brain injury[J]. Cell Mol Neurobiol, 2003, 23(4-5):539-50.
[41] Wrana JL.,Attisano L, Wieser Rotraud. Mechanism of activation of the TGF-β receptor. Nature, 1994, 370(4):341-347.
[42]Clawson, T.F., Vannucci, S.J.,Wang, G.M.,et al. Hypoxia-ischemia-induced apoptotic cell death correlates with IGF-I mRNA decrease in neonatal rat brain [J]. Biol Signals Recept, 1999 , 8(4-5):281-93.
[43] Beilharz EJ, Russo VC, Butler G. Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury[J]. Brain Res Mol Brain Res, .1998 , 59(2):119-34.
[44] Yamaguchi F, Itano T, Miyamoto O. Increase of extracellular insulin-like growth factor I (IGF-I) concentration following electrolytical lesion in rat hippocampus [J]. Neurosci Lett, 1991, 128(2):273-6.
[45] Beilharz EJ, Williams CE, Dragunow M. Mechanisms of delayed cell death following hypoxic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss[J]. Brain Res Mol Brain Res, 1995, 29(1):1-14.
[46] Pons S, Torres-Aleman I. Basic fibroblast growth factor modulates insulin-like growth factor-I, its receptor, and its binding proteins in hypothalamic cell cultures [J]. Endocrinology,1992,131(5):2271-8.
[47]Lee WH,Bondy C.Insulin-like growth factors and cerebral ischemia[J].Ann N Y Acad Sci,1993,679:418-22.
[48]Guan J,Bennet L,Gluckman PD.Insulin-like growth factor-1 and post-ischemic brain injury[J].Prog Neurobiol,2003,70(6):443-462.
[49]Tagami M,Yamagata K,Nara Y.Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats[J].Lab Invest,1997,76(5):603-612.
[50]Guan J,Bennet TL,George S.Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep[J].Neuroscience,2000,95(3):831-9.
[51]Tamm I,Kikuchi T.Insulin-like growth factor-1(IGF-1),insulin,and epidermal growth factor(EGF) are survival factors for density-inhibited,quiescent Balb/c-3T3murine fibroblasts[J].J Cell Physiol,1990,143(3):494-500.
[52]D'Mello SR,Borodezt K,Soltoff SR Insulin-like growth factor and potassium depolarization maintain neuronal survival by distinct pathways:possible involvement of PI 3-kinase in IGF-1 signaling[J].J Neurosci,1997,17(5):1548-1560.
[53]Parrizas M,LeRoith D.Insulin-like growth factor-1 inhibition of apoptosis is associated with increased expression of the bcl-xL gene product[J].Endocrinology,1997,138(3):1355-1358.
[54]Nicholas RS,Stevens S,Wing MG.Microglia-derived IGF-2 prevents TNFalpha induced death of mature oligodendrocytes in vitro[J].J Neuroimmunol,2002,124(1-2):36-44.
[55]Guan J,Williams CE,Skinner SJ.The effects of insulin-like growth factor (IGF)-1,IGF-2,and des-IGF-1 on neuronal loss after hypoxic-ischemic brain injury in adult rats:evidence for a role for IGF binding proteins[J].Endocrinology,1996,137(3):893-8.
[56]Cowell RM,Plane JM,Silverstein FS.Complement activation contributes to hypoxic-ischemic brain injury in neonatal rats[J].J Neurosci,2003,23(28):9459-9468.
[57]Devlin LA,Nguyen MD,Figueroa E,et al.Effects of endotoxin administration and cerebral hypoxia-ischemia on complement activity and local transcriptional regulation in neonatal rats[J] Neurosci Lett, 2005, 390(2): 109-113.
[58] Ten VS, Sosunov SA, Mazer SP,et al. C1q-deficiency is neuroprotective against hypoxic-ischemic brain injury in neonatal mice[J]. Stroke, 2005 , 36(10):2244-50.
[59] Grether JK, Nelson KB, Dambrosia JM,et al. Interferons and cerebral palsy. J Pediatr, 1999,134(3):324-32.
[60] Sonntag J, Wagner MH, Strauss E,et al. Complement and contact activation in term neonates after fetal acidosis[J]. Arch Dis Child Fetal Neonatal Ed, 1998 , 78(2):F125-8.
[61] Zhang ZG, Chopp M. Zaloga C, et al. Cerebral endothelial nitric oxide synthase expression after fotal cerebral ischemia in rats[J] . Stroke , 1993 , 24(12):2016-2021 .
[62] AmerF, Samdani, Ted M, Dawson, et,al. Nitric oxide synthase in models of focal ischemia[J]. Stroke, 1997, 28(6): 1283-1288.
[63] Nagayama M, Zhang F, Iadecola C. Delayed treatment with aminoguanidine decreases focal cerebral ischemic damage and enhances neurologic recovery in rats[J]. J Cereb Blood Flow Metab, 1998, 18(10): 1107-1113.
[64] Choi DW. Nitric Oxide: Foe Of friend to the injured brain[J]. ProcNatlAcad Sci U S A, 1993, 90(21):9741-9743.
[65] Iadecola C, Zhang F, Xu S,et al. Inducible nitric oxide synthase gene expression in brain following cerebral ischemia[J]. J Cereb Blood Flow Metab, 1995, 15(3):378-84.
[66] Beasley TC, Bari F, Thore C,et al. Cerebral ischemia/reperfusion increases endothelial nitric oxide synthase levels by an indomethacin-sensitive mechanism [J]. J Cereb Blood Flow Metab, 1998, 18(1):88-96.
[67] Liesz A, Suri-Payer E, Veltkamp C,et al. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke [J]. Nat Med, 2009, 15(2): 192-9.
[68]Brittis PA, Flanagan JG. Nogo domains and a Nogo receptor: implicationsfor axon regeneration[J]. Neuron, 2001, 30(1): 11-4.
[69] Fenghua HU, Betty P, Stephane B, et al. Nogo-A interacts with the Nogo-66 receptor through multiple sites to create an isoform -selective subnanornolar agonist[J]. J Neurosci, 2005, 25(22): 5298-5304.
[70] Jin WL, Liu YY, Liu HL, el al. Intraneuronal localization of Nogo-A in the rat. [J]. J Comp Neurol, 2003, 458(1):1-10.
[71] Josephson A, Trifunovski A, Scheele C,et al. Activity-induced and developmental downregulation of the Nogo receptor[J]. Cell Tissue Res, 2003, 311(3):333-42.
[72] Oertle, T., Schwab, M. E., et al.Nogo and its partners[J]. TrendsCell Biol.,2003, 13(4):187-194.
[73] Li, Q., Qi, B., Oka, K., Shimakage,M. et al. Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer[J]. Oncogene 2001, 20(30), 3929-3936.
[74] Meier S, Brauer AU, Heimrich B,et al. Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure[J]. FASEB J., 2003 , 17(9): 1153-5.
[75] Huber AB, Weinmann O, Brosamle C,et al. Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions [J]. J Neurosci, 2002 , 22(9):3553-3567.
[76] Kim JE, Bonilla IE, Qiu D,et al. Nogo-C is sufficient to delay nerve regeneration[J]. Mol Cell Neurosci. 2003, 23(3):451-459.
[77] Schachner M, Bartsch U. Multiple functions of the myelin-associated glycoprotein MAG (siglec-4a) in formation and maintenance of myelin. [J], Glia, 2000, 29(2): 154-165.
[78] Mukhopadhyay G, Dohe～y P, Walsh FS, et al . A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron, 1994, 13(3):757-767.
[79] Wang KC, Koprivica V, Kim JA,et al. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth[J]. Nature , 2002 , 417(6892):941-944.
[80] Jean WC, Spellman SR, Nussbaum ES, et al. Reperfusion injury after focal cerebral ischemia : the role of inflammation and the therapeutic horizon [J]. Neurosurgery, 1998, 43(6): 1382-1396.
[81] Nurden AT, Bihour C, Macchi L, et al. Platelet activation in thrombotic disorders[J]. NouvRev FrHematol, 1993, 35(1): 67-71.
[82] Turowski P, Adamson P, Greenwood J. Pharmacological targeting of ICAM-1 signaling in brain endothelial cells: potential for treating neuroinflammation[J]. 2005, 25(1): 153-170.
[83] Krupinski J, Kaluza J, Kumar P,et al. Role of angiogenesis in patient with cerebral ischemic stroke.Stroke, 1994, 25(9):1794-1798.
[84] Lau D, Mollnau H, Eiserich JP, et al. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc Natl Acad Sci U S A, 2005, 102(2):431-436.
[85] Vestweber D, Blanks JE. Mechanisms that regulate the function of the selectins and their ligands[J]. Physiol Rev, 1999, 79(1): 181-213.
[86] Cherian P, Hankey GJ, Eikelboom JW,et al. Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes[J]. Stroke, 2003, 34(9):2132-2137.
[87] Milner R, Campbell IL. The extracellular matrix and cytokines regulate microglial integrin expression and activation[J]. J Immunol, 2003, 170(7):3850-3858.
[88] Mousa SA.av vitronectin receptors in vascular-mediated disorders[J]. Medicinal Res Rev, 2003, 23(2): 190-199.
[89] Celtik C, Acunas. B, Oner N,et al. Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy[J]. Brain Dev, 2004, 26(6):398-402.
[90] Lima JE, Takayanagui OM, Garcia LV. Use of Neuron-specific enolase for assessing the severity and outcome in patients with neurological disorders[J]. Braz J Med Biol Res, 2004, 37(1): 19-26.
[91] Csrcia-Alix, Cabanas F, Pellicer A, et al. Neuron-specific enolase and myelin basic protein: Relationship of cerebrospinal fluid condition of asphyxiated full-term infants[J].Pediatrics,1994,93(2):234-240.
[92]Nagdyman N,K(o|¨)men W,Ko HK,M(u|¨)ller C,Obladen M.Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia[J].Pediatr Res,2001,49(4):502-506.
[93]Vannucci RC,Perlman JM.Interventions for perinatal hypoxic-ischemic encephalopathy[J].Pediatrics,1997,100(6):1004-1014.
[94]Lorek A,Takei Y,Cady EB,Wyatt JS,Penrice J,Edwards AD,et al.Delayed (secondary) cerebral energy failure after acute hypoxiaischemia in the newborn piglet:continuous 48-h studies by phosphorus magnetic resonance spectroscopy[J].Pediatr Res,1994,36(6):699-706.
[95]Barone FC,Clark RK,Price WJ,et al.Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia[J].Brain Res,1993,623(1):77-82.
[96]Thoresen M.Cooling the newborn after asphyxia-physiological and experimental background and its clinical use[J].Semin Neonatol,2000,5(1):61-73.
[97]Verdu Perez A,Falero MP,Arroyos A,et al.Blood neuronal specific enolase in newborns with perinatal asphyxia[J].Rev Neurol,2001,32(8):714-717.
[98]邓辉,唐从海等.NBNA评分对新生儿缺氧缺血性脑病预后评估应用的临床意义[J].实用医技杂志,2008,15(18):2405-2406.
[99]黄燕萍,李小权等.神经元特异性烯醇酶在早期评估新生儿缺氧缺血性脑病预后中的价值[J].新生儿科杂志,2005,20(1):23-26.
[100]晁占湖,王有福等.NBNA评分筛查足月高危儿脑损伤及早期干预的临床应用[J].中国实用神经疾病杂志,2008,11(1):84-87.