In vivo evidence that erythropoietin has a neuroprotective effect during subarachnoid hemorrhage

To ascertain in vivo whether recombinant human erythropoietin has a neuroprotective effect on the cortex during subarachnoid hemorrhage, 56 rabbits were divided into the following groups: Group 1 control sham operated plus placebo (n=14; saline solution - NaCl 0.9%); Group 2 control sham operated plus recombinant human erythropoietin (n=14); Group 3 subarachnoid hemorrhage plus placebo (n=14); Group 4 subarachnoid hemorrhage plus recombinant human erythropoietin (n=14; intraperitoneal administration of recombinant human erythropoietin immediately after inducing subarachnoid hemorrhage). In none of the Groups 1 and 2 animals was subarachnoid hemorrhage induced. In Group 3 rabbits, an increase in locomotor activity (open field apparatus) was observed 24, 48 and 72 h after surgery, and the mortality rate was 42.9% within 72 h after surgery, and, no increase in locomotor activity was observed in Group 4 rabbits, which survived for at least 72 h. Our findings suggest that recombinant human erythropoietin may be of benefit in the treatment of subarachnoid hemorrhage.     

The effect of EGb-761 on morphologic vasospasm in canine basilar artery after subarachnoid hemorrhage

This study investigated the effects of Ginkgo biloba extract (EGb-76l), an anti-oxidant and platelet-activating factor antagonist, on basilar artery vasospasm in an experimental canine subarachnoid hemorrhage model. Morphometric analyses were performed, and serum and cerebrospinal fluid endothelin-l levels were measured by radioimmunoassay. Comparisons were made between treated and untreated groups. Twenty-four mongrel dogs were randomly assigned to three groups. The animals in group 1 (n = 8) were not subjected to subarachnoid hemorrhage and received no treatment. In this group, serum and cerebrospinal fluid endothelin-l levels were measured daily for 8 days. On day 9, the animals were killed and their basilar arteries were excised for histopathological examination. In group 2 (n = 8), subarachnoid hemorrhage was produced using autologous arterial blood, and daily intravenous boluses of saline were administered for the next 8 days. Assessments of endothelin-l levels and the basilar arteries were performed as described for group 1. In group 3 (n = 8), subarachnoid hemorrhage was produced using autologous arterial blood, and daily intravenous boluses of EGb-761 were administered for 8 days. Endothelin-1 levels and the basilar arteries were assessed as described above. The groups' serum endothelin-1, cerebrospinal fluid endothelin-1, and histopathological findings were compared.In group 1, the serum and cerebrospinal fluid endothelin-1 levels did not change significantly over the 8 days, and histopathological examination of the basilar arteries revealed no abnormalities. In group 2, the serum and cerebrospinal fluid endothelin-1 levels increased abruptly and significantly on day 2, and remained high to the end of the study period (day 8). Histopathological examination revealed marked vasospasm. In group 3, the serum and cerebrospinal fluid endothelin-1 levels followed the same pattern observed in group 2; however, the arteries showed significantly less vasospasm than that observed in group 2.The study findings did not provide information about the mechanism of action of the platelet-activating factor-antagonist EGb-761, but they clearly show that this agent decreases morphologic vasospasm in the dog basilar artery.     

脑脊液置换联用尼莫地平治疗蛛网膜下腔出血临床观察

目的观察脑脊液置换联用尼莫地平治疗蛛网膜下腔出血临床疗效。方法53例SAH患者随机分为2组,对照组给予内科常规治疗,治疗组为内科常规治疗、脑脊液置换联用尼莫地平。结果治疗组较对照组头痛缓解时间明显缩短(P<0.05);脑血管痉挛和脑积水的并发征发生率显著减少(P<0.05);再出血的发生率差异无统计学意义(P>0.05)。结论脑脊液置换联用尼莫地平治疗蛛网膜下腔出血可缓解头痛,减少并发症。     

动脉瘤性蛛网膜下腔出血后脑血管痉挛67例临床分析

目的 分析脑脊液置换联合尼莫地平防治动脉瘤性蛛网膜下腔出血（aSAH）后脑血管痉挛（CVS）的效果。方法 aSAH患者67例随机分为两组,对照组常规治疗,观察组在常规治疗基础上行脑脊液置换术。观察两组DCVS和继发性脑梗死的发生率及临床疗效及大脑中动脉平均血流速度。结果 观察组总有效率明显高于对照组,大脑中动脉流速明显低于对照组（P〈0.05）。结论 脑脊液置换联合尼莫地平可明显降低动脉瘤性蛛网膜下腔出血患者迟发型脑血管痉挛的发生,降低大脑中动脉的平均血流速度。     

蛛网膜下腔出血后迟发性脑血管痉挛中 TNF-α和NF-кB 的表达变化

目的：检测蛛网膜下腔出血（以下简称 SAH）后迟发性脑血管痉挛中TNF-α和NF-кB的表达变化。方法56只中国白兔随机分成3组：对照组（ n ＝8）：不做枕大池穿刺注血,处死;SAH组（ n ＝24）：在第0天和第2天分二次枕大池注射自体动脉血,分别在第1次注血后第4天、第7天和第14天分三批处死,每组8只;假手术组（ n＝24）：只做枕大池穿刺不注血,第4天、第7天和第14天处死,每组8只。通过计算动脉口径比判断基底动脉痉挛程度,使用免疫组化和免疫蛋白印迹的方法检测迟发性脑血管痉挛中TNF-α和NF-кB的表达变化。结果枕大池注血方法可以造成SAH后迟发性脑血管痉挛模型。 NF-κB 和 TNF-α在注血后第4天表达开始增加（ P ＜0．01）,在第7天达到最高值（ P ＜0．01）,第14天降到对照组水平。结论蛛网膜下腔出血后迟发性脑血管痉挛中NF-κB及 TNF-α表达增加,炎症反应在此过程中起着重要作用。     

不同置换量对蛛网膜下腔出血脑脊液置换疗效的影响

目的 观察不同置换量对蛛网膜下腔出血脑脊液置换疗效的影响。方法 将60例患者随机分为A组（大量脑脊液置换组）30例、B组（小量脑脊液置换组）30例。对A、B组腰椎穿刺用三通管行脑脊液置换，置换总量A组50～70ml做，B组10～30ml／次。结果头痛缓解时间A组〈B组（P〈0．01）；继发脑血管痉挛、脑积水的发生率A组〈B组（P〈0．05），但再出血的发生率两组差异无显著意义（P〉0．05）；总有效率A组〉B组（P〈0．05）。结论 早期大量脑脊液置换治疗蛛网膜下腔出血的效果优于小量脑脊液置换，但都不能减少再出血的发生。     

大承气汤联合脑脊液置换治疗蛛网膜下腔出血的疗效观察

目的观察大承气汤联合脑脊液置换治疗蛛网膜下腔出血的临床效果。方法将临床确诊为蛛网膜下腔出血的患者60例随机分为两组,在常规内科药物治疗的基础上,治疗组加用大承气汤服用,同时行脑脊液置换治疗。结果治疗组疗效优于对照组,治疗组头痛缓解时间、脑脊液变清时间、头颅CT改变时间及住院时间均明显缩短（P〈0.05）。两组在各种常见并发症的发生率及治疗有效率上差异均有统计学意义（P〈0.05）。结论大承气汤联合脑脊液置换治疗蛛网膜下腔出血能显著改善患者的临床症状,促进血肿吸收,减少并发症,提高疗效。     

The inhibitory effects of cholalic acid and hyodeoxycholalic acid on the expression of TNFα and IL-1β after cerebral ischemia in rats

Previous studies have shown that Qing Kai Ling, a traditional Chinese medicine, was able to effectively prevent the inflammation from cerebral ischemia (Chen et al., 2002). The cholalic acid and hyodeoxycholalic acid (cholalic acid mixture) was major active components in Qing Kai Ling. To study the effects of cholalic acid mixture on the damage cascade of cerebral ischemia, rat model of focal cerebral ischemia was established by permanent occlusion of left middle cerebral artery. We found that the administration of cholalic acid mixture could reduce the ischemic infarct size after 24 h of ischemia, and cholalic acid mixture could be detected in cerebrospinal fluid after 2h of administration. We also found that the concentrations of tumor necrosis factor-alpha and interlukin-1beta in rat brain were significantly lower when compared to the untreated animals after 12 h and 24 h of ischemia. The concentrations of von Willebrand factor and neuron specific enolase in the plasma were remarkably decreased in cholalic acid mixture treated animals than in the untreated ones after 12h of ischemia. Our results suggested that cholalic acid mixture is able to decrease the expression of inflammation factors including tumor necrosis factor-alpha and interlukin-1beta after focal cerebral ischemia. These two authors contribute equally to the paper.     

蛛网膜下腔出血行腰椎穿刺置管持续稳压引流的疗效分析

目的探讨腰椎蛛网膜下腔置管持续引流对蛛网膜下腔出血(SAH)的疗效。方法:对63例SAH患者进行治疗:治疗组(33例)实施腰椎蛛网膜下腔置管持续流脑脊液,对照组(30例)行间断腰椎穿刺放脑脊液。结果:治疗组头痛或轻程度,痊愈率明显优于对照组,脑血管痉挛、脑积水发生率明显低于对照组,未增加再出血、脑疝发生率及病死率。结论:腰椎蛛网膜下腔置管持续稳压引流脑脊液是一种安全、有效的治疗SAH的方法。     

Prostaglandin metabolism and prostacyclin in cerebral vasospasm

1. Contractions of isolated human pial arteries, induced either by exposition to hemorrhagic cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage and cerebral vasospasm or by exposition to noradrenaline, were markedly augmented after preincubation of the vessel segments with the cyclooxygenase inhibitor indomethacin, while serotonin-induced contractions were unaffected. 2. Prostacyclin relaxed human pial arteries contracted by either PGF2 alpha, noradrenaline, serotonin or hemorrhagic CSF. The same though less marked effects were obtained with 6-keto-PGE1. 3. The results support the contention that an intact vascular prostacyclin synthesis is important for the maintenance of a normal cerebrovascular tone, and that disturbances of the prostaglandin metabolism may be a prerequisite for the development of arterial spasm after aneurysmal subarachnoid hemorrhage. Tentatively. 4. a prostacyclin deficiency may be involved in the pathogenesis of delayed cerebral vasospasm after subarachnoid hemorrhage.     

脑脊液置换治疗蛛网膜下腔出血42例疗效观察

目的探讨脑脊液置换术治疗蛛网膜下腔出血的临床效果。方法 73例蛛网膜下腔出血患者随机分为治疗组42例及对照组31例。治疗组在常规治疗的基础上进行脑脊液置换术治疗,对照组行常规治疗。结果两组体征的改变情况、并发症发生情况、治疗效果总有效率治疗组均优于对照组,两组差异有统计学意义。结论脑脊液置换术治疗蛛网膜下腔出血,能减少脑血管痉挛,脑积水,脑梗死等并发症,有利于患者恢复,操作简单易行、安全,疗效显著,值得推广。     

腰椎穿刺引流脑脊液治疗动脉瘤性蛛网膜下腔出血的临床效果分析

目的 探讨持续腰椎穿刺引流脑脊液治疗动脉瘤性蛛网膜下腔出血的临床效果.方法 选择2006年1月至2013年6月入住解放军第一四八医院、郑州大学第二附属医院神经内科的305例动脉瘤性蛛网膜下腔出血患者,按随机数字表将患者随机分为研究组（152例）和对照组（153例）.研究组患者给予标准治疗＋腰椎穿刺引流脑脊液,对照组只进行标准治疗.观察2组迟发性缺血性神经功能缺损的发生率和临床改善情况.结果 研究组和对照组迟发性缺血性神经功能缺损的发生率分别为21.1％ （32/152）和36.6％ （56/153）,组间差异有统计学意义（P=0.018）.研究组患者24 h平均引流脑脊液（135±14）ml,平均引流时间（5.2±1.1）d.研究组局灶性缺血者和意识障碍者占比明显低于对照组[8.5％ （13/152）比20.9％（32/153）,7.2％（11/152）比9.2％ （14/153）]（P=0.015,P=0.036）,脑梗死发生率低于对照组[23.3％（35/152）比31.2％ （48/153）] （P=0.036）,需要持续脑脊液腹腔分流者占比低于对照组[4.6％（7/152）比7.8％ （12/153）] （P =0.024）.在第10天和6个月,研究组改良的Rankin评分0～2分者占比分别为55.3％（84/152）和81.6％（124/152）,而对照组分别为34.6％ （53/153）和80.4％（123/153）,第10天组间差异有统计学意义（P =0.007）.结论 动脉瘤性蛛网膜下腔出血后持续腰椎穿刺引流脑脊液能降低迟发性缺血性神经功能缺损的发生率,改善早期临床结果,但对出血后6个月时的临床结果无明显影响.     

降纤酶对大鼠局灶性脑缺血的影响

目的 :观察降纤酶 (defibrase)对大鼠局灶性脑缺血性损伤的治疗作用。方法 :雄性Wistar大鼠 ,采用大脑中动脉内线栓法诱导局灶性脑缺血 ,60只局灶性脑缺血大鼠 ,随机分成 1 0组 ,每组 6只 ,其中 5组大鼠分别在缺血后 0 .5 ,3 ,6,9,1 2h静脉注射降纤酶 ,8U·kg-1,另 5组大鼠分别在相同时间点静脉注射等量生理盐水对照 ,另设 1 0鼠作假手术组。各组大鼠均在手术后 2 4h进行神经功能评分 ,然后处死大鼠 ,标本用苏木精曙红染色 (HE)及氯化三苯基四氮唑(TTC)染色 ,观察梗死灶大小、病理改变。结果 :缺血后 0 .5 ,3h静脉给药治疗组神经功能评分比对照组明显改善 ,分别为 (0 .8±s 0 .5 )分 ,(1 .3± 0 .5 )分和 (3 .0± 0 .9)分 ,(3 .2± 1 .0 )分 ,脑梗死灶体积比对照组明显减小 ,分别为 (1 1 9±3 9)mm3 ,(1 41± 62 )mm3 和 (2 91± 5 6)mm3 ,(2 97± 3 9)mm3 ,差别有非常显著意义 (P <0 .0 1 ) ;缺血区病理改变也轻于对照组。缺血后 6,9,1 2h给药组神经功能评分、脑梗死灶体积与对照组比较均无明显差异 (P >0 .0 5 ) ,治疗组与对照组镜下均见点状出血 ,但未发现治疗组增加脑梗死后出血率。结论 :早期静脉应用降纤酶有效缩小脑梗死灶体积 ,且不增加出血率。     

Effects of erythropoietin on blood-brain barrier disruption in focal cerebral ischemia

This study was performed to test whether systemically administered erythropoietin (EPO) could attenuate the blood-brain barrier (BBB) disruption in focal ischemia. Rats were injected intraperitoneally with 2,500 IU/kg of recombinant human EPO or normal saline 24 h before middle cerebral artery (MCA) occlusion. The transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid was determined to measure the degree of BBB disruption 1 h after MCA occlusion. In the control animals, the Ki of the ischemic cortex (IC) was significantly higher than that of the contralateral cortex (CC; +128%, p = 0.0002). In the EPO-treated animals, the Ki of the IC was not significantly different from that of the CC and was significantly lower (-44%, p = 0.003) than that of the control animals. Our data suggest that MCA occlusion increased BBB disruption, and the disruption was attenuated with EPO pretreatment.     

Penetration of cefotaxime into human cerebrospinal fluid

The penetration of cefotaxime (CTX) into the cerebrospinal fluid (CSF) was monitored to evaluate the prophylactic efficacy of the drug against post-craniotomy infections. Doses ranged from 1 to 2 g were administered to patients with subarachnoid hemorrhage due to the rupture of cerebral aneurysm, traumatic cerebral contusion, or subdural edema accompanied by intracerebral hemorrhage, by intravenous drip infusion over a period of 30 or 60 minutes. CTX readily entered the CSF with concentrations exceeding MICs against the major pathogens occurring after craniotomy. CTX proved to be effective in the prevention of post-craniotomy infections in noninflammatory situations, especially after surgery in the case of cerebral traumas or subarachnoid hemorrhage.     

尼莫地平治疗蛛网膜下腔出血的系统评价

目的：系统评价尼莫地平治疗蛛网膜下腔出血的疗效和安全性。方法：计算机检索Cochrane图书馆、Pubmed、EMbase、ISI、中国生物医学文献数据库（CBM）、中国期刊全文数据库（CNKI）、中文科技期刊全文数据库（VIP）、万方数字化期刊全文库以及中国生物医学文献服务系统,纳入尼莫地平与安慰剂治疗蛛网膜下腔出血的随机对照试验（RCT）、系统评价和Meta分析,对纳入的RCT进行方法学质量评价,采用RevMan5．0软件进行系统评价。结果：共纳入8项研究,合计2223例患者。Meta分析结果显示,2组死亡率比较差异无统计学意义[RR=0．67,95％CI（0．44,1．03）,P=0．07],尼莫地平组在预防脑缺血方面优于对照组,2组比较差异有统计学意义[RR=0．57,95％CI（0．42,0．78）,P=0．0004],2组不良反应发生率比较差异无统计学意义。结论：尼莫地平能够安全、有效地预防蛛网膜下腔出血患者脑缺血的发生,但在降低死亡率方面没有明显的优势。     

L-精氨酸对大鼠蛛网膜下腔出血脑组织血供的改善作用

目的　探讨L 精氨酸 (L Arg)对蛛网膜下腔出血(SAH)后继发性脑缺血的影响。方法　用血管内脑底动脉环穿刺法建立大鼠SAH模型 ,将动物分为假手术 (SO)组、SAH组和SAH +L Arg组。L Arg于术前 3 0min按 50 0mg·kg- 1ip ,每 6h追加 1次。动态检测 2 4h内大脑顶叶皮层局部脑血流量 (rCBF) ,测定不同时间点血清一氧化氮 (NO ,NO-2 /NO-3 )水平 ,同时监测血压和血气。结果　假手术对rCBF和血清NO含量无显著影响。SAH组术后rCBF迅速降低并持续 2 4h ;SAH组血清NO水平于术后 1h开始下降 ,持续 2 4h ;与SAH组比较 ,SAH +L Arg组rCBF下降的速度减慢且程度减轻 ;血清NO水平下降的程度减轻。结论　L Arg可部分补偿SAH后血清NO不足 ,从而缓解继发性脑缺血程度     

Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil

Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents.     

经鼻小剂量重组人促红细胞生成素对脑缺血大鼠脑内基质金属蛋白酶-9小窝蛋白-1表达的影响

目的探讨重组人促红细胞生成素(rhEPO)鼻腔给药对急性脑缺血大鼠脑内基质金属蛋白酶-9(MMP-9)、小窝蛋白-1(CAV-1)表达的影响。方法雄性SD大鼠54只,随机分为假手术组、缺血组和rhEPO组。采用线栓法制作大鼠永久性局灶性脑缺血(pMCAO模型)。rhEPO组在缺血1h后经鼻腔给予48UrhEPO,缺血组和假手术组1h后给予等体积的生理盐水。24h后断头取脑,分别用干湿质量法计算脑组织含水量,2,3,5-氯化三苯基四氮唑(TTC)法测量脑梗死体积,免疫组织化学方法测定MMP-9、CAV-1的表达。结果鼻腔给药治疗组与缺血组相比,脑组织含水量减少,脑梗死体积减小,MMP-9的表达降低,而CAV-1的表达升高(P<0.05)。结论 rhEPO降低了急性脑缺血大鼠脑内MMP-9蛋白的表达,增高了CAV-1的表达,对缺血脑组织具有脑保护作用。     

Alpha-adrenoceptors in human and animal cerebral arteries: alterations after sympathetic denervation and subarachnoid hemorrhage

Vasospasm of cerebral arteries in patients with subarachnoid hemorrhage frequently presents severe clinical problems resulting from cerebral ischemia, but the pathogenesis of vasospasm is still poorly understood. The contractile response of human cerebral arteries to noradrenaline is larger than the responses in other species. Neurogenic factors controlling brain circulation may play an important role in pathological conditions such as subarachnoid hemorrhage. Motohatsu Fujiwara and colleagues review species variations of alpha-adrenoceptors in cerebral arteries and their alterations after surgical sympathectomy. They compare these changes to those occurring in human cerebral arteries following subarachnoid hemorrhage and discuss their relationship to vasospasm.