一氧化氮在蛛网膜下腔出血后脑血管痉挛中的作用

脑血管痉挛(cerebral vasospasm,CVS)是动脉瘤性蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后高致死率、致残率的主要原因之一。SAH后CVS的发病机制尚不明确,目前比较肯定的机制是蛛网膜下腔血液和红细胞崩解产物氧合血红蛋白(OxyHb)是CVS发生的第一推动力,起关键作用。血管     

蛛网膜下腔出血后脑血管痉挛发病机制的研究新进展

蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后,患者常伴有脑血管痉挛(cerebral vasospasm,CVS),出血后4～14d为高峰期.CVS导致脑组织局部缺血,进而引起神经功能障碍.近年来有大量文献资料和实验数据表明SAH后CVS的发生率约30％～80％,约46％的患者出现临床症状,是导致SAH患者死亡或致残的主要并发症[1].其病因机制复杂,研究表明多种因素与CVS的发生有关.本文就SAH后CVS发病机制的研究进展综述如下.     

大鼠脑血管痉挛活体动物模型

脑血管痉挛（cerebral vasospasm，CVS）是蛛网膜下腔出血（subarachnoid hemorrhage，SAH）的主要并发症，其发生机制尚不明确，活体动物实验是目前研究的焦点。大鼠是较为常用的研究CVS的实验动物，因为其具有其它动物无法比拟的优点，主要表现在（1）大鼠SAH模型表现出CVS两个阶段的变化，与人类相似；（2）大鼠模型能显示与人类相似的脑动脉血管病理变化；（3）大鼠与人类有很高的基因同源性，能更好地研究SAH后CVS相关分子水平的变化；（4）大鼠价格便宜，更容易饲养。     

自由基清除剂对减少大鼠SAH后CVS的研究

目的 通过建立大鼠蛛网膜下腔出血模型并应用自由基清除剂对其进行治疗,观察大鼠脑基底动脉的病理变化及其管壁上细胞间粘附因子1（ICAM-1）、白介素6（IL-6）在治疗前、后的动态变化,为进一步明确脑血管痉挛（cerebral vasospasm,CVS）的发病机制及治疗脑血管痉挛提供理论依据.方法 取Sprague Dawley （SD）大鼠98只,观察正常大鼠及治疗大鼠SAH前后基底动脉管径的变化;行免疫组化染色对大鼠脑基底动脉进行免疫学检测,观察ICAM-1、IL-6在血管壁上表达的动态变化;行原位杂交检测观察大鼠脑基底动脉管壁上ICAM-1、IL-6在分子水平表达的动态变化.结论 ①自由基清除剂能够抑制SAH后CVS的免疫炎症反应;②应用自由基清除剂对防治CVS有一定效果,能够有效缓解CVS.     

经颅多普勒超声诊断自发性蛛网膜下腔出血后脑血管痉挛

<正>自发性蛛网膜下腔出血(subarachnoid hemorrhage,SAH)常由脑动脉瘤破裂导致,出血引致颅底脑池内颈内动脉、椎基底动脉及其分支为主的脑血管痉挛(cerebral vasospasm,CVS),并因此出现迟发性缺血性脑损伤。上述血管痉挛常常在发病后就开始存在,于发病后1 w达高峰期,是SAH致残和死亡的重要原因。CT动脉成像(computer tomography     

蛛网膜下腔出血后脑血管痉挛中钾通道的研究进展

脑血管痉挛（cerebral vasospasm，cvs）是蛛网膜下腔出血（subarachnoid hemorrhage，SAH）后高致死率、致残率的主要原因之一，发生率约为45％。过去数十年来国内外学者们做了大量动物实验和临床试验，从细胞、分子水平对CVS的发病机制进行了论述，然而至今仍未完全阐明。目前，普遍认为SAH后CVS是由多因素所致，可能与内皮的损伤、平滑肌细胞内离子泵功能的紊乱和蛋白激酶（PKC）的激活、血管壁炎症反应以及血管细胞的增殖等有关。二十世纪八十年代以来，随着分子生物学技术的发展，以及电压钳和单细胞通道记录等新技术的应用，医学界对钾通道的认识逐渐深入，在钾离子生理药理的研究领域特别是钾通道开放剂的开发项目上屡有重大突破，而后者也有望成为继钙通道阻滞剂后又一通过作用于离子通道而改善血管痉挛的临床用药。本文结合国内外最新相关文献报道，主要就SAH后钾通道的生理状态与CVS之间关系的研究进展做一综述。     

蛛网膜下腔出血后炎症反应的研究进展

正蛛网膜下腔出血(subarachnoid hemorrhage,SAH)病死率和致残率均较高。目前,临床上仍缺乏能明显改善病人预后的治疗手段,因为SAH的损伤机制较为复杂,包括早期脑损伤(early brain injury,EBI)、迟发性脑损伤(delayed brain injury,DBI)、脑血管痉挛(cerebral vasospasm,CVS)和全身炎症反应综     

中英文对照名词词汇（四）

脑深部电刺激术 deep brain stimulation（DBS） 脑血管痉挛 cerebral vasospasm（CVS） 脑血流量 cerebral blood flow（CBF） 脑血流自动调节 cerebral autoregulation（CA） 脑氧饱和度cerebral oxygen saturation（ScO2）     

动脉瘤性蛛网膜下腔出血后抗血管痉挛的药物治疗

正蛛网膜下腔出血(su[barachnoid hemorrhage,SAH)的年发病率为9/10万1],占所有脑卒中的[2]2]3%。颅内动脉瘤破裂是自发性SAH的主要原因[,而动脉瘤破裂后脑血管痉挛(cerebral vasospasm,[3,4C]VS)是导致SAH患者死亡、严重残疾的主要因素。因此,动脉瘤破裂出血后抗CVS的治疗尤为重要。本文总结动脉瘤性SAH后CVS药物治疗现状及最新进展,以提高对CVS的认识,并为临床治疗提供参考。     

CT灌注成像在动脉瘤性蛛网膜下腔出血中的 临床应用进展

正脑血管痉挛(cerebral vasospasm,CVS)和迟发性脑缺血(delayed cerebral ischemia,DCI)是动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoidhemorrhage,a SAH)最常见的两大并发症。传统的观念认为,CVS是导致DCI的主要甚至唯一原因。但是,越来越多的证据表明,单纯用CVS无法完全解释DCI和预后不良。微循环障碍、微血栓形成、血液黏     

脑血管痉挛血管壁损害的发病机制研究

迟发性脑血管痉挛是蛛网膜下隙出血的一种常见并发症。目前,其确切发生机制还不完全清楚。近年来,一些学者发现,蛛网膜下隙出血后血管壁发生了器质性病理变化,伴随蛛网膜下隙出血的免疫炎性反应、血管壁细胞增殖与凋亡导致的血管壁的损害可能是脑血管痉挛发生的关键病理途径。本文就其研究的相关进展进行总结。     

Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: methodological analysis

The transgenic mouse has been used to study subarachnoid hemorrhage (SAH) induced delayed cerebral vasospasm (DCV). Methodological parameters have not been analyzed to validate this model and associated neurological deficits have not been described. We introduce a technique to quantify DCV and associated neurological deficits. C57BL/6J mice were subjected to SAH or sham surgery. Seventy-two hours later, the vasculature was cast in situ with India ink/gelatin at perfusion pressures of 40-60, 60-80, or 100-120 mmHg. Mice were perfused with and without microfiltration. Additional mice underwent grading of SAH size, measurement of vascular diameters, and neurological examination (score range 5-27; 27= normal). When cast at 60-80 mmHg, SAH was associated with an intraluminal cross-sectional diameter reduction in 3 of 7 ipsilateral vascular segments. At 40-60 mmHg, the diameter of only one segment was reduced. No changes were observed at 100-120 mmHg. Emboli prevented adequate perfusion of vascular segments in the absence of microfiltration. Median (interquartile range) neurologic score was reduced after SAH (sham, 27(27); SAH 11(7-17)). Deficits correlated with middle cerebral artery (MCA) diameter and SAH grade. MCA diameter also correlated with SAH grade. Only when utilizing microfiltration, controlling for hemorrhage size, and casting at perfusion pressures of 60-80 mmHg does India ink/gelatin vascular casting demonstrate consistent DCV that correspnds to neurological deficits. This allows measurement of both anatomical and clinical DCV in the mouse.     

大鼠蛛网膜下腔出血后迟发性脑血管痉挛和血管壁增殖关系的实验研究

目的探讨大鼠蛛网膜下腔出血(SAH)后迟发性脑血管痉挛(DCV)的发生和血管壁增殖之间的关系。方法SD大鼠78只,随机分为SAH组(A组,36只)、生理盐水组(B组,36只)和正常对照组(C组,6只)。A组采用枕大池二次注血法建立SAH模型,B组同法注射等量生理盐水。A、B组分别在首次注血(或生理盐水)后4、7、10、13、16、20d取基底动脉(BA)行HE染色后测量其内径周长、血管壁厚度,观察血管结构改变;免疫组化染色后检测BA增殖细胞核抗原(PCNA)蛋白表达。结果B、C组BA血管结构正常、无DCV发生,A组第4天出现DCV,第7天达到高峰,高峰期持续至第10天,后逐渐缓解,20d基本恢复正常;A组除20d外,各时相有不同程度的内膜增厚皱折、平滑肌层增厚等改变。PCNA在B组及C组BA中无表达,A组各时相均有表达,第7天有较强表达(P<0.05)。结论SAH后DCV的发生和严重程度与血管壁增殖程度密切相关。     

Mouse model of subarachnoid hemorrhage associated cerebral vasospasm: Methodological analysis

Abstract

The transgenic mouse has been used to study subarachnoid hemorrhage (SAH) induced delayed cerebral vasospasm (DCV). Methodological parameters have not been analyzed to validate this model and associated neurological deficits have not been described. We introduce a technique to quantify DCV and associated neurological deficits. C57BL/6J mice were subjected to SAH or sham surgery. Seventy-two hours later, the vasculature was cast in situ with India ink/gelatin at perfusion pressures of 40-60, 60-80, or 100- 120 mmHg. Mice were perfused with and without microfiltration. Additional mice underwent grading of SAH size, measurement of vascular diameters, and neurological examination (score range 5-27; 27 = normal). When cast at 60-80 mmHg, SAH was associated with an intraluminal cross-sectional diameter reduction in 3 of 7 ipsilateral vascular segments. At 40-60 mmHg, the diameter of only one segment was reduced. No changes were observed at 100-120 mmHg. Emboli prevented adequate perfusion of vascular segments in the absence of microfiltration. Median (interquartile range) neurologic score was reduced after SAH (sham, 27 (27); SAH 11 (7-17)). Deficits correlated with middle cerebral artery (MCA) diameter and SAH grade. MCA diameter also correlated with SAH grade. Only when utilizing microfiltration, controlling for hemorrhage size, and casting at perfusion pressures of 60-80 mmHg does India ink/gelatin vascular casting demonstrate consistent DCV that correspnds to neurological deficits. This allows measurement of both anatomical and clinical DCV in the mouse. [Neurol Res 2002; 24: 510-516]     

大鼠蛛网膜下腔出血后迟发性脑血管痉挛和rHSG表达相关性的实验研究

目的 探讨大鼠蛛网膜下腔出血(SAH)后迟发性脑血管痉挛(DCV)和大鼠增殖抑制基因(rHSG)表达之间的关系.方法 SD大鼠156只,随机分为SAH组(A组)、生理盐水组(B组)和正常对照组(C组).A组采用枕大池二次注血法诱发;B组同法注射等量生理盐水.A、B组分别在4、7、10、13、16、20d取基底动脉(BA)行HE染色后测量其内径周长、血管壁厚度,观察血管结构改变;免疫组化检测BA rHSG蛋白;RT-PCR法检测BA中rHSG mRNA.结果 B、C组BA血管结构正常,无DCV发生;A组第4天出现DCV,第7天达到高峰,高峰期持续至第10天.后逐渐缓解,20d趋于正常.A组除20d外,各时相BA有不同程度的内膜增厚皱折、平滑肌层增厚等增殖性改变.与B组及C组相比,A组4～16d rHSG蛋白及rHSG mRNA表达均降低(P<0.05),第7天显著降低(P<0.05).结论 SAH后DCV的发生和严重程度与血管壁增生程度及rHSG低表达密切相关.     

Effect of cilostazol on delayed cerebral vasospasm after subarachnoid hemorrhage in rats: evaluation using black blood magnetic resonance imaging

The purpose of this study was to use black blood magnetic resonance imaging (BB-MRI) to assess delayed cerebral vasospasm (DCV) after subarachnoid hemorrhage (SAH) in rats, and evaluate whether delayed treatment with the anti-platelet agent cilostazol was effective on DCV. BA vasospasm was sequentially assessed at 1, 2, and 3 h, and 1-6 days after SAH by BB-MRI. BB-MRI clearly visualized biphasic vasospasm; early vasospasm at 1 h later and the maximal DCV at day 2. Cilostazol was perorally administered twice at day 1 after having confirmed significant DCV using BB-MRI. The effect of cilostazol on DCV was evaluated at day 2. Cilostazol significantly attenuated DCV and suppressed the levels of malondialdehide and 8-isoprostane in CSF after SAH. This study shows that BB-MRI is a useful and less invasive method for the evaluation of DCV, and cilostazol may be effective on DCV.     

高压氧对蛛网膜下腔出血后脑血管痉挛的影响

目的探讨高压氧（hyperbaric oxygen,HBO）对蛛网膜下腔出血（SAH）后迟发性脑血管痉挛的影响及机制。方法采用枕大池2次注血法建立迟发性脑血管痉挛模型,将60只模型动物随机等分为SAH组和SAH＋HBO组,用显微测量法测量基底动脉管径,比色法测定血清中一氧化氮（NO）及一氧化氮合酶（NOS）含量,原子吸收分光光度计测定脑组织中的Ca^2＋含量。结果模型制作成功后96h测量基底动脉直径,结果显示：经HBO治疗后,脑血管痉挛的程度明显缓解。SAH组NO、NOS含量在术后24h及96h均降低,而经HBO治疗后则增高。SAH组Ca^2＋含量在术后24h及96h增高,经HBO治疗后则降低。结论高压氧能够缓解SAH后脑血管痉挛程度,改善受损的脑功能。     

内源性血红素氧合酶-1在脑血管痉挛中作用机制的实验研究

目的探讨内源性血红素氧合酶(HO-1)在迟发性脑血管痉挛(DCV)中的作用。方法 SD大鼠108只,随机分为生理盐水组(A组)、蛛网膜下腔出血(SAH)组(B组)、和SAH+氯高铁血红素(Hemin)组(C组)。采用枕大池二次注血法建立SAH模型,于注血后3d、5d、7d,取基底动脉(BA)测量其内径周长、血管壁厚度,观察血管结构改变,免疫组化染色检测BA中HO-1蛋白表达,RT-PCR检测BA中HO-1 mRNA的表达水平。结果A组BA血管结构正常,未发生DCV;B组第3天有DCV、第7天达到高峰;C组大鼠BA痉挛情况较B组明显缓解(P<0.01)。免疫组化显示A组大鼠BA上无HO-1蛋白表达;B组大鼠BA上HO-1蛋白低表达;C组大鼠BA上HO-1蛋白高表达,B、C两组比较有显著性差异(P<0.01)。RT-PCR显示A组大鼠BA无HO-1 mRNA的表达;B组大鼠BA上HO-1 mRNA低表达;C组大鼠BA HO-1mRNA高表达;B、C两组比较有显著性差异(P<0.01)。结论 HO-1诱导剂hemin可诱导HO-1过度表达并防止SAH后DCV的发生。     

不同浓度氧合血红蛋白对大鼠蛛网膜下腔出血后迟发性脑血管痉挛的影响

目的 观察不同浓度氧合血红蛋白对大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后迟发性脑血管痉挛(delayed cerebral vasospasm,DCV)的影响.方法 将24只大鼠分为三组,对照组(8例)、动脉血SAH组(8例)、静脉血SAH组(8例),分别用枕大池二次注血法将0.3...     

An overview of new pharmacological treatments for cerebrovascular dysfunction after experimental subarachnoid hemorrhage

Cerebral vasospasm and the resulting cerebral ischemia occurring after subarachnoid hemorrhage (SAH) are still responsible for the considerable morbidity and mortality in patients affected by cerebral aneurysms. Mechanisms contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia after SAH have been intensively investigated in recent years. It has been suggested that the pathogenesis of vasospasm is related to a number of pathological processes, including endothelial damage, smooth muscle cell contraction resulting from spasmogenic substances generated during lyses of subarachnoid blood clots, changes in vascular responsiveness and inflammatory or immunological reactions of the vascular wall.A great deal of experimental and clinical research has been conducted in an effort to find ways to prevent these complications. However, to date, the main therapeutic interventions remain elusive and are limited to the manipulation of systemic blood pressure, alteration of blood volume or viscosity, and control of arterial dioxide tension.Even though no single pharmacological agent or treatment protocol has been identified which could prevent or reverse these deadly complications, a number of promising drugs have been investigated. Among these is the hormone erythropoietin (EPO), the main regulator of erythropoiesis. It has recently been found that EPO produces a neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is systemically administered.This topic review collects the relevant literature on the main investigative therapies for cerebrovascular dysfunction after aneurysmal SAH. In addition, it points out rHuEPO, which may hold promise in future clinical trials to prevent the occurrence of vasospasm and cerebral ischemia after SAH.