U74389G预防狗蛛网膜下腔出血后脑血管痉挛

颅内动脉瘤破裂后的主要并发症包括蛛网膜下腔出血（ＳＡＨ）本身所引起的脑损害以及蛛网膜下腔出血后第７天所发生的脑血管痉挛。其发生机理为：颅内动脉瘤破裂后，去氧自由基通过直接作用于动脉壁而导致血管痉挛；此外，还可引起蛛网膜下腔红细胞脂氧化而诱发血管收缩。Ｕ７４３８９Ｇ是一种有力的脂氧化抑制剂和去氧自由基清除剂。本研究验证了去氧自由基和脂氧化在实验性狗蛛网膜下腔出血中引起血管痉挛的相关作用。１６只狗实验前均进行了脑血管造影，于第２天将新鲜血液注入到延髓池诱发蛛网膜下腔出血。随机将１６只狗分为两组：第一…     

尼莫地平对大鼠脑血管痉挛缺血性脑损害的防治作用

目的：探讨尼莫地平（ＮＤ）对蛛网膜下腔出血（ＳＡＨ）后脑血管痉挛（ＣＶＳ）缺血性脑损害的保护作用。方法：应用非开颅大鼠模型,观察ＳＡＨ组和ＮＤ处理组２４ｈ内微区脑血流量（ＣＢＦ）和海马组织Ｃａ含量动态变化及３天后海马ＣＡ１区形态学改变。结果：在ＳＡＨ后２４ｈ内,ＳＡＨ组ＣＢＦ明显而持续降低,海马组织Ｃａ含量逐渐增加,３天后海马ＣＡ１区神经元明显受损。ＮＤ使上述改变均减轻。结论：ＮＤ通过对微循环的改善增加ＳＡＨ后ＣＶＳ时ＣＢＦ,通过阻断脑缺血时的有害代谢环节而减轻ＣＶＳ缺血性神经元损伤。     

内皮素与外伤后迟发性缺血性脑损害

内皮素是一种由２１个氨基酸组成的血管活性多肽，包括ＥＴ－１、ＥＴ－２和ＥＴ－３三种类型，其中ＥＴ－１由血管内皮细胞产生。多种化学或物理因素对ＥＴ的合成和分泌起调节作用，血管平滑肌中有ＥＴ－Ａ和ＥＴ－Ｂ两种受体，ＥＴ－１选择性作用于ＥＴ－Ａ受体引起血管收缩。在蛛网膜下腔出血（ＳＡＨ）后的脑血管痉挛中，ＥＴ－Ａ受体介导的血管收缩起了重要作用。ＥＴ－１和ＥＴ－Ａ受体结合后通过激活平滑肌细胞膜上的ＰＩＰ２系统、Ｌ型Ｃａ２＋通道和Ｎａ＋／Ｈ＋交换等一系列信号系统而发挥作用。脑外伤后，机体的应激反应、血管内皮细胞损伤、出血、缺血、缺氧均可使ＥＴ的合成和释放增加，进而导致脑血管痉挛，发生迟发性缺血性脑损害。     

山莨菪碱对蛛网膜下腔出血后基底动脉产生EDRF的作用及抗…

用山莨菪碱（６５４－２）防治蛛网膜下腔出血（ＳＡＨ）后脑血管痉挛，观察６５４－２对基底动脉中ＥＤＲＦ，ＭＤＡ，ＳＯＤ，ｃＧＭＰ，Ｃａ＾２＋，Ｎａ＾２＋的影响。结果表明，应用６５４－２后降低了基底动脉中ＭＤＡ产生及Ｃａ＾２＋Ｎａ＾＋的含量，与ＳＡＨ组比，ＥＤＲＦ释放增加，ＳＯＤ活性及ｃＧＭＰ水平提高，基底动脉内皮细胞受到保护，基底动脉收缩幅度减小。提示，６５４－２可通过保护内皮细胞，减轻氧自由基损伤     

蛛网膜下腔出血后脑血管痉挛平滑肌超微结构研究

采用盐酸和胶原酶消化动脉外膜的技术，对正常的脑动脉、蛛网膜下腔出血后痉挛的脑动脉及经前列腺素F2α(prostaglandin F2α，PGFZa)处理的脑动脉平滑肌细胞构筑进行研究。结果显示正常平滑肌细胞是梭形的，沿着血管长轴环行分布，细胞间通过突起相连，肌细胞外膜面通常是光滑的；痉挛的脑动脉和经PGF2α处理的脑动脉平滑肌外膜面均出现非常相似的膜皱折和卷曲，肌间隙增宽。透射电镜显示急性痉挛管壁病理变化轻微；迟发性痉挛出现明显病理性超微结构改变。实验结果提示急性脑血管痉挛是由平滑肌收缩引起，病理变化轻微；迟发性脑血管痉挛是血管持久收缩伴病理性超微结构改变。     

血一氧化氮和内皮素含量变化在大鼠急性脑血管痉挛中的作用

目的：探讨一氧化氮（ＮＯ）,内皮素（ＥＴ）在蛛网膜下腔出血（ＳＡＨ）后急性脑血管痉挛（ＣＶＳ）中的作用。方法：应用非开颅大鼠ＳＡＨ模型,检测ＳＡＨ前后基底动脉（ＢＡ）管径改变,２４ｈ内大鼠顶叶皮层局部脑血流量,血中ＮＯ,ＥＴ含量动态变化。     

山莨菪碱对蛛网膜下腔出血后基底动脉产生EDRF的作用及抗痉挛机制研究

用山莨菪碱（６５４－２）防治蛛网膜下腔出血（ＳＡＨ）后脑血管痉挛，观察６５４－２对基底动脉中ＥＤＲＦ，ＭＤＡ，ＳＯＤ，ｃＧＭＰ，Ｃａ￣（２＋），Ｎａ￣＋的影响。结果表明，应用６５４－２后降低了基底动脉中ＭＤＡ产生及Ｃａ￣（２＋）Ｎａ￣＋的含量，与ＳＡＨ组比，ＥＤＲＦ释放增加，ＳＯＤ活性及ｃＧＭＰ水平提高，基底动脉内皮细胞受到保护，基底动脉收缩幅度减小。提示，６５４－２可通过保护内皮细胞，减轻氧自由基损伤，拮抗Ｃａ￣（２＋）Ｎａ￣＋在细胞内的蓄积，从而促进内皮细胞ＥＤＲＦ释放，引起血管舒张，明显减轻ＳＡＨ后的脑血管痉挛。     

不同年龄的正常和高血压大鼠脑动脉内弹性膜的变化

运用图像分析仪、光镜和电镜，对不同年龄组的４０只自发性高血压和１９只京都纯种大鼠的脑动脉内弹性膜（Ａ１）、管壁（Ａ２）和管腔（Ａ３）进行了观察测定，发现高血压鼠和正常鼠比较，脑动脉最显著的变化表现为：内弹性膜变薄、折叠减少，部分断裂以及中膜平滑肌的退变，内弹性膜与管壁的比值（ＲＡＴＥ，即Ａ１／Ａ２）显著减小（Ｐ＜０．０１），而壁与腔的比（ＲＡＴＥ２，Ａ２／Ａ３）无显著变化。前者可能与高血压脑血管脆     

多膜下腔出血后脑血管痉挛平滑肌超微结构研究

采用盐酸和胶原酶消化动脉外膜的技术,对正常的脑动脉、蛛网膜下腔出血后痉挛的脑动脉及经前列腺素Ｆ２α（ｐｒｏｓｔａｎｇｌａｎｄｉｎ Ｆ２α,ＰＧＦ２α）处理的脑动脉平滑肌细胞构筑进行研究。结果显示：正常平滑肌细胞是梭形的,沿着血管长轴环行分布,细胞间通过突起相连,肌细胞外膜面通常是光滑的,痉挛的脑动脉和经ＰＧＦ２α处理的脑动脉平滑肌外膜面均出现非常相似的膜皱折和卷曲,缺间隙增宽。透射电镜显示急性痉挛     

阿斯匹林与动脉瘤性蛛网膜下腔出血后迟发性脑缺血

０１４阿斯匹林与动脉瘤性蛛网膜下腔出血后迟发性脑缺血［英］／ＪｕｖｅｌｄＳ／／ＪＮｅｕｒｏｓｕｒｇ．－１９９５，８２（６）．－９４５～９５２动脉瘤性蛛网膜下腔出血（ＳＡＨ）致残率和死亡率均很高，主要原因是ＳＡＨ后的血管痉孪，而ＳＡＩ后脑血管痉挛及迟发...     

Inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway attenuates cerebral vasospasm following experimental subarachnoid hemorrhage in rabbits

The p38 mitogen-activated protein kinase (MAPK) plays an important role in apoptosis and is also involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Here, we sought to examine whether inhibition of p38 MAPK could attenuate cerebral vasospasm and investigate the underlying mechanisms in a rabbit SAH model. SAH was established in rabbits (n=12/group) using the double-hemorrhage method. We observed apparent vasospasm in the basilar arteries of rabbits with SAH, which was significantly attenuated by SB203580, a selective p38MAPK inhibitor. Immunoblotting assays showed enhanced phosphorylation of p38 MAPK and ATF2 and increased caspase-3 cleavage following SAH, which were, however, markedly suppressed by SB203580. TUNEL staining further revealed significant apoptosis in the basilar arteries of rabbits with SAH, which was scantly present in rabbits treated with SB203580. Our results demonstrated that p38 MAPK was activated in cerebral vasospasm and associated with increased apoptosis in the basilar arteries and p38 MAPK inhibition suppressed apoptosis, suggesting that p38 MAPK could be a novel therapeutic target for cerebral vasospasm.     

Enhanced vasoconstrictor effect of endothelin in cerebral arteries from rats with subarachnoid haemorrhage

The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline-injected controls. Endothelin elicited concentration-dependent contractions of rat basilar artery segments. The endothelin-induced contractions were much stronger in the SAH compared to control animals, which suggests a role in the pathophysiology of cerebral vasospasm.     

钩藤碱减轻大鼠蛛网膜下腔出血后脑血管痉挛

目的 探讨钩藤碱（Rhy）能否减轻大鼠蛛网膜下腔出血（SAH）后的脑血管痉挛（CVS）及其机制。 方法 成年雄性SD大鼠,采用血管内刺破法建立SAH模型。SAH后立即腹腔注射Rhy,24h后通过磁共振成像（MRI）测量基底动脉(BA)直径。BA经HE染色后,测量BA的直径和血管壁厚度;应用Western blotting和免疫荧光染色检测不同组动物BA的磷酸化p38丝裂原活化蛋白激酶（p-p38MAPK）、p-p53和剪切Caspase-3（cleaved-Caspase-3）蛋白的表达水平。结果 MRI和组织学染色结果均表明,10mg/kgRhy在SAH后可明显增加BA的直径并显著减少血管壁厚度（P<0.05）。Rhy明显降低了SAH后BA的p-p38MAPK、p-p53和cleaved-Caspase-3蛋白的表达水平（P<0.05）。Rhy能够明显减少SAH后BA内皮细胞p-p38MAPK、p-p53和cleaved-Caspase-3等凋亡蛋白的表达。结论 Rhy能通过抑制BA内皮细胞凋亡减轻SAH后脑血管痉挛的严重程度。     

Endothelial injury following experimental subarachnoid hemorrhage in rats: Effects on brain blood flow

Background: The leading cause of death and disability in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is cerebral vasospasm, a persistent, progressive, and often irreversible constriction of cerebral arteries. A wide array of pathological changes occur in cerebral arteries following SAH, with endothelial injury being the earliest and most consistent one. Since intact endothelium modulates many reflexes that influence vascular tone, damage to them may represent a significant contributor to cerebral vasospasm. Methods: Changes in local cerebellar blood flow (LCBF) and pathological alterations in major cerebral arteries were studied and compared in rats at various time intervals following SAH. SAH induced by the subarachnoid injection of 0.3 ml of whole blood. Sham rats received a subarachnoid injection of 0.3 ml of isotonic saline. Results: Except for an immediate but transient decrease, LCBF remained unchanged over a 3 day period following saline injection. Likewise, there were no pathological alterations in cerebral arteries of saline-injected rats. In contrast, the subarachnoid injection of whole blood produced significant changes in both LCBF and cerebral arteries. Within 30 minutes postblood injection, LCBF became significantly decreased and remained so for 4 hours. However, within 24 hours, LCBF had returned to control levels where it remained for 3 days. Endothelial injury was observed in the basilar and middle cerebral arteries from 30 minutes through 4 hours, the same periods in which LCBF was significantly reduced. Within 24 hours, the time period in which LCBF had rebounded to control ranges, cerebral arteries showed no evidence of endothelial damage and resembled control cells. Conclusion: The results indicate a direct correlation between changes in LCBF and the structural integrity of endothelial cells in the early stages following SAH. The lack of chronically depressed LCBF (after 1 day) may be related to the quick structural repair of endothelium. © 1994 Wiley-Liss, Inc.     

大鼠蛛网膜下腔出血脑微区血流量与血清一氧化氮变化

目的探讨蛛网膜下腔出血（ＳＡＨ）后继发性脑缺血损害及其一氧化氮（ＮＯ）的作用。方法应用非开颅性方法建立大鼠ＳＡＨ模型,检测２４ｈ内脑微区血流量和颅内血清ＮＯ的动态改变,并测量基底动脉（ＢＡ）管径。结果ＳＡＨ后脑微区血流量迅速降低,１ｈ达最低值,２４ｈ内无明显恢复趋势（Ｐ＜ ０．０１）。ＳＡＨ后１ｈ血清ＮＯ开始减低,井持续２４ｈ（Ｐ＜０．０１）。ＢＡ管径于ＳＡＨ后明显缩小（Ｐ＜０．０１）。结论ＳＡＨ时脑灌注压降低、脑血管痉挛及微循环异常均可能与脑血流量降低有关。ＮＯ减少是脑血管 痉挛和微循环异常发生的重要因素之一。     

实验性大鼠脑血管痉挛动物模型制备

目的探索实验性SD大鼠蛛网膜下隙出血（SAH）脑血管痉挛模型制备方法。方法尾动脉取血,立体定位仪下枕大池二次注血,印度墨水灌注测量大脑中动脉、颈内动脉和基底动脉直径,Morris水迷宫行为学测试,测定血中内皮素-1、一氧化氮合酶含量。结果 SAH组脑血管明显变细,Morris水迷宫显示有学习记忆能力减退,大脑中动脉、颈内动脉和基底动脉直径分别为（169.33±8.67）mm、（227.33±14.25）mm、（226.33±5.99）mm;内皮素-1和一氧化氮合酶分别为（214.36±10.49）g/L、（211.15±16.99）U/mL,与对照组比较有统计学差异。结论本实验方法能够制备蛛网膜下隙出血后脑血管痉挛模型。     

Mitofusin-2在大鼠蛛网膜下腔出血后大脑动脉内表达的变化

目的 研究Mitofusin-2(Mfn2)在大鼠蛛网膜下腔出血（SAH）后大脑动脉中表达的变化,寻找Mfn2基因与脑血管痉挛(CVS)之间的关系。 方法 蛛网膜下腔出血模型由刺破颈内动脉的颅内动脉分叉处诱导。146只SD大鼠被随机分为6组：假手术组（sham组）,SAH后24h、48h、72h、7d 和14d各组。计算动物死亡率,测定神经功能学评分及脑水含量。组织学检测观察形态学变化,采用Western blotting及RT-PCR 分别检测SAH后不同时间点的大鼠主要大脑动脉Mfn2蛋白及mRNA 水平的表达变化。 结果 围绕在基底动脉周围的血块随着时间逐渐消失,形态学观察显示SAH 24h组基底动脉出现严重的痉挛。SAH7d组的基底动脉中层无阳性的免疫组织化学阳性染色。Western blotting结果显示,Mfn2蛋白表达 sham组与SAH48h组和SAH72h组相比,均显著增加(P<0.05),SAH 7d出现显著性降低(P<0.05),SAH14d 恢复至 sham 和SAH24h 组水平。而mRNA 水平变化与蛋白水平变化相类似。Mfn2基因参与到SAH后血管的自我调节过程中,表达随着时间增加而增加,并在72h到达高峰,7d时显著下降,14d左右恢复至sham组水平。 结论 Mfn2在SAH后的早期以及迟发型脑血管痉挛中起重要作用,为揭示SAH后脑血管痉挛的机理提供实验依据。     

Morphological changes of cerebral arteries in a canine double hemorrhage model

Cerebral vasospasm is a major cause of morbidity and mortality in patients suffering from subarachnoid hemorrhage (SAH). Despite numerous studies, the pathogenesis of this deadly disorder is not clearly understood. Alterations in endothelial cells are a distinct morphological feature of cerebral vasospasm and some recent studies suggest that apoptosis might play a role in the cells' death. The goal of the present study is to examine the time course of apoptosis in endothelial cells of spastic cerebral arteries following experimental subarachnoid hemorrhage. Fifteen dogs were used in the present study. Twelve of them were divided into three groups (four per group) and subjected to a double-hemorrhage method of SAH. Following SAH, groups were sacrificed respectively on days 3, 5, and 7. Three dogs served as controls without blood injection. The basilar arteries were studied with the transmission electron microscopy and with angiography. Angiographic vasospasm began on day 3 and peaked on day 7. In morphologic studies, control dogs did not demonstrate apoptotic-like changes in endothelial cells of the basilar arteries. Beginning with day 3, apoptotic-like changes were noted in endothelial cells and consisted of condensation of peripheral nuclear chromatin, blebbing of the cell membrane, and condensation of the cytoplasm. Such changes progressed with time and were maximally developed by day 7. This is the first study that demonstrates the time course of apoptotic-like changes in the endothelial cells in the vasospastic basilar artery. Apoptosis might play an important role in the pathogenesis of vasospasm.     

Preventive effects of intracisternal alphatochopherol on cerebral vasospasm in experimental subarachnoid haemorrhage

Vasospasm is an important cause of morbidity and/or mortality with a subarachnoid haemorrhage (SAH). The roles of lipid peroxidation in a vasospasm caused by a SAH remain to be investigated. The effect of an intracisternal administration of alphatochopherol on a cerebral vasospasm was investigated in an experimental model. The authors assessed whether the administration of alphatochopherol reduced the vasospasm. By means of an intracisternal blood injection model, a SAH was induced in 30 rats, which were randomly divided into three groups, as follows: group I (G1), without a SAH and drug, group II (G2), a SAH alone, group III (G3), a SAH and alphatochopherol. Following the withdrawal of cerebrospinal fluid (CSF), a fresh unheparinized arterial blood was injected into the cisterna magna to induce a SAH. In G3, 20 U (0.4ml) alphatochopherol was intracisternally injected forty-five hours after induction of the SAH. All rats were sacrificed 72 hours after the induction. The basilar artery, with surrounding tissue, was removed from the cranium. The cross-sectional diameter of the lumen and vessel wall of the rat basilar artery was assessed from a planimetric analysis, and changes compared with G1 and G2. The reduction in the luminal cross-sectional diameter of the vessels exposed to subarachnoid blood was found to be 29.01 % (p=0.001). The group treated with alphatochopherol had a 9% reduction (p=0.004). The role of lipid peroxidation on a vasospasm caused by SAH is well known to be critical. Data from the present study indicated that antioxidant therapy, with topical alphatochopherol, may be promising on a vasospasm caused by a SAH.     

The influence of subarachnoid hemorrhage on neurons: an animal model

Subarachnoid hemorrhage (SAH) has considerable mortality and morbidity, but the pathophysiologic mechanism is not entirely clear. Following SAH, blood or its lysate enters the subarachnoid space. This study examined how blood lysate influences the vulnerable brain following SAH. Heparinized hemolysate was slowly injected into the cisterna magna of 10 female rabbits, while a control group of 10 rabbits received a similar injection of heparinized isotonic sodium chloride solution without hemolysate. The basilar artery and brain tissue were excised after perfusion fixation. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of the basilar artery, and brain damage was investigated by TUNEL staining. In the SAH group, the apoptosis index of neuronal cells located at the base of the temporal lobe averaged 26% (range = 3 to 56%), which was significantly higher than the corresponding apoptosis index in the control group (mean 0.5%, range = 0 to 4%, p <0.001). The mean cross-sectional area of the basilar artery in the SAH group did not differ significantly from that in the control group. These results suggest that SAH induces apoptosis of neuronal cells by a mechanism that is independent of cerebral vasospasm.