蜂花烧烫伤膏对烧伤大鼠血管内皮细胞的保护作用研究

目的:研究蜂花烧烫伤膏对烧伤大鼠血管内皮细胞的保护作用,探讨其治疗烧烫伤的作用机制。方法:热水烧伤法建立大鼠30%TBSA深Ⅱ度烧伤模型。造模成功后随机分为对照组、烧伤延迟复苏组、京万红组与蜂花烧烫伤膏组,分别立即给予相应干预,并比较烫伤后1 h、3 h、6 h、12 h、24 h和48 h的肿瘤坏死因子-α(TNF-α)、内皮素(ET-1)、一氧化氮(NO)与ET-1/NO比值水平。结果:与对照组大鼠比较,烧伤延迟复苏组TNF-α、ET-1与ET-1/NO比值在伤后1 h即明显升高,12 h达高峰后逐渐下降;NO的含量在伤后1h即显著升高,6 h达高峰后逐渐下降;48h后仍与对照组有较大差异。与烧伤延迟复苏组比较,蜂花烧烫伤膏组各时相点的TNF-α、ET-1、NO和ET-1/NO比值均显著降低,但变化趋势基本一致。结论:蜂花烧烫伤膏通过降低TNF-α、ET-1和NO水平,优化ET-1/NO系统,起到保护烧伤大鼠血管内皮细胞的作用。     

糖尿病大鼠海马中NO含量的变化

目的观察糖尿病大鼠海马中NOS表达及NO含量的变化,研究糖尿病对海马的影响。方法用Wista大鼠,共24只,随机分成2组,正常组12只,糖尿病组12只,糖尿病组用STZ制模,满12周后,取脑应用生物化学方法、免疫组化及Westernblot技术对大鼠海马进行观察。结果糖尿病组大鼠海马NOS的表达及NO含量较正常组增高(P<0·05)。结论糖尿病可引起海马的病理改变。     

一氧化氮、内皮素-1对大鼠肢体缺血/再灌注后脑损伤的影响

目的: 研究一氧化氮(NO)和内皮素-1(ET-1)在大鼠肢体缺血/再灌注(LI/R)后脑损伤中的作用,探讨NO/ET-1平衡关系的变化对脑损伤的影响.方法: 在大鼠LI/R损伤模型上,应用NO合成前体物质L-精氨酸(L-Arg)、一氧化氮合酶(NOS)抑制剂氨基胍(AG)、ETA受体阻断剂BQl23进行干预,观察血浆 NO、ET-1、MDA、XOD、SOD、LDH及脑组织tNOS、iNOS、cNOS、NO、ET-1、MDA、XOD、MPO、 SOD的变化.结果: 与对照组比较,I/R组血浆MDA、XOD、LDH及脑组织MDA、XOD、MPO升高,SOD活性降低(P<0.01),脑组织tNOS和iNOS明显升高,而cNOS明显降低(P<0.01),I/R组血浆及脑组织NO、ET-1增加,NO/ET-1比值降低,脑损伤加重.应用L-Arg及BQ123后,血浆及脑组织NO/ET-1比值较I/R组升高,脑损伤减轻,应用AG后,NO/ET-1比值降低,脑损伤进一步加重.结论: 肢体缺血/再灌注后,一氧化氮与内皮素-l的比值降低时脑损伤加重.     

促红细胞生成素对脑缺血/再灌注损伤的保护作用

目的:探讨促红细胞生成素(Epo)对大鼠脑缺血/再灌注损伤的保护作用。方法:32只SD大鼠,采用夹闭双侧颈总动脉30min再灌注24h制作脑缺血/再灌注模型。随机分为4组(n=8):假手术组、脑缺血/再灌注组、Epo组及阳性对照组(尼莫地平),观察缺血/再灌注后血清一氧化氮(NO)和脑组织匀浆中超氧化歧化酶(SOD)活性、丙二醛(MDA)含量及脑组织含水量的变化。结果:Epo组血清NO和脑组织匀浆中MDA含量显著下降,SOD活性显著升高,脑组织含水量显著下降,与缺血/再灌注组相比有显著性差异。结论:大鼠脑缺血/再灌注后,Epo能减轻脑组织的含水量,减少自由基的生成,减轻脂质过氧化反应,对脑缺血/再灌注损伤有保护作用。     

表没食子儿茶素没食子酸酯对蛛网膜下腔出血大鼠脑损伤的保护作用研究

目的:探讨表没食子儿茶素没食子酸酯(EGCG)对蛛网膜下腔出血(SAH)脑损伤的影响及其可能机制。方法:选取健康雄性Sprague-Dawley(SD)大鼠80只,按照随机数字表法分为假手术组(Sham组)、SAH组、SAH+EGCG组、蛛网膜下出血+生理盐水组(SAH+NS组),每组各20只。SAH造模成功后1d、3d,检测大鼠神经功能评分及脑组织含水量;造模成功3d后,脑组织石蜡切片HE染色观察脑细胞形态,并采用超敏C-反应蛋白(hs CRP)试剂盒检测血清hs CRP水平,通过Western blotting检测脑组织脑源性神经生长因子(brain derived neurotrophic factor,BDNF)及与其高度亲和的酪氨酸激酶受体B(tropomyosin-related kinase B,TrkB)的表达。结果:(1)SAH+EGCG组神经功能评分较Sham组明显降低,但较同期SAH组增高明显(P0.05);(2)与Sham组比较,SAH+EGCG组脑组织含水量明显增加,但与同期SAH组比较,SAH+EGCG组脑组织含水量明显降低(P0.05);(3)与SAH组比较,SAH+EGCG组血清hs CRP水平明显降低(P0.05);(4)与SAH组比较,SAH+EGCG组脑组织石蜡切片HE染色神经细胞水肿明显减轻,且坏死神经元减少,细胞核固缩明显减轻;(5)与SAH组比较,SAH+EGCG组脑组织BDNF、TrkB的表达量明显升高(P0.05)。结论:EGCG能够有效的保护大鼠SAH后的脑损伤,促进神经功能修复,减轻预后神经功能障碍,可能与其促进脑组织BDNF、TrkB的表达有关。     

脑不对称性对Balb/c小鼠海马 IL-6水平的影响

研究了Balb/c小鼠海马内细胞因子白细胞介素 6 (interleukin 6 ,IL 6 )含量与脑不对称的关系。实验采用伸爪取食法将小鼠区分为左利、右利和双利鼠 ,分别于腹腔注射细菌脂多糖 (Lipopolysaccharide,LPS)或无菌生理盐水 (Saline ,NS) ,2h后快速断头 ,冰上快速分离两侧海马 ,制备海马脑组织匀浆 ,用ELISA法测定海马中IL 6蛋白含量。结果表明 :正常对照组中海马IL 6水平为右利鼠明显高于左利鼠 (P =0 0 0 1) ,左利鼠又明显高于双利鼠 (P =0 0 0 1) ,两侧海马之间无明显差别 ;注射LPS 2h后 ,海马IL 6总体水平没有变化 ,只在右利小鼠右侧海马IL 6含量明显升高 (P <0 0 5 ) ,明显高于左利 (P <0 0 0 1)和双利 (P <0 0 0 1) ,双利Balb/c小鼠两侧海马IL 6水平明显低于右利和左利小鼠。上述结果提示 ,在正常生理状态下及LPS刺激后引起的海马IL 6水平变化均与脑不对称性有关     

大鼠脑缺血／再灌注损伤中一氧化氮和一氧化氮合酶的变化

目的:探讨脑缺血/再灌注损伤中脑组织一氧化氮和一氧化氮合酶的变化.方法:用线栓法建立大脑中动脉梗死(MCAO)模型,观察局灶性脑缺血30 min再灌注30 min、1 h、3 h、 6 h、12 h、24 h、48 h 、72 h、96 h、168 h NO含量和NOS活性的变化.结果:脑缺血/再灌注过程中NO含量和NOS活性呈"双峰样"改变.缺血/再灌注30 min后NO含量和NOS活性升高,再灌注3 h时NO含量和NOS活性下降,再灌注6 h、12 h、24 h、48 h 、72 h NO含量和NOS活性再次显著升高,与再灌注72 h达峰值.结论:NO和NOS通过多种途径参与了脑缺血/再灌注损伤的病理过程.     

甲状腺素对动脉瘤性蛛网膜下腔出血大鼠脑缺氧诱导因子-1α表达的影响及其机制*

目的:探讨甲状腺素(T4)对动脉瘤性蛛网膜下腔出血后大鼠脑缺氧诱导因子-1α(HIF-1α)表达的调节及其机制。方法:72只雄性成年SD大鼠随机分为以下4组:蛛网膜下腔出血模型组(SAH)(n=18)、蛛网膜下腔出血+甲状腺素组(SAH+T4)(n=18)、蛛网膜下腔出血+溶剂组(SAH+溶剂组)(n=18)、假手术组(n=18)。颈内动脉穿刺法建立蛛网膜下腔出血的模型,术后行颅脑CT平扫,建模后立即开始给药,按3 μg/100 g腹腔注射,每隔24 h一次,连续3 d,SAH+T4组予甲状腺素干预,SAH+溶剂组予等体积溶剂干预,均在建模后72 h处死;各组6只大鼠经多聚甲醛灌注处死后石蜡包埋切片行免疫组化染色检测HIF-1α及p-Akt蛋白、6只用TUNEL法检测凋亡,6只用干湿重法做脑水肿含量检测。结果:建模成功后SAH组及SAH+T4组、SAH+溶剂组大鼠的脑组织肿胀明显,蛛网膜下腔可见暗红色血凝块。SAH组神经行为学评分、脑含水量、凋亡率、HIF-1α蛋白、p-Akt蛋白均较假手术组明显增高(P＜0.05);SAH+T4组神经行为学评分、HIF-1α蛋白、p-Akt蛋白均较SAH组明显增高,其脑含水量、凋亡均较SAH组明显减少(P＜0.05)。结论:使用T4替代治疗可以上调动脉瘤性蛛网膜下腔出血后大鼠脑HIF-1α蛋白表达水平,可能是通过激活三磷酸肌醇激酶／蛋白激酶B(PI3K/Akt)信号通路,使凋亡率减小,最终大鼠行为学得以改善,对大鼠脑产生保护作用。     

NG-硝基-L-精氨酸对大鼠局灶性缺血脑区线粒体损伤的影响

目的:观察非选择性一氧化氮合酶抑制剂NG-硝基-L-精氨酸(NG-nitro-L-arginine,L-NA)对局灶性脑缺血大鼠脑线粒体的损伤作用,以探讨其改善缺血性脑损伤的作用机制。方法:将大鼠随机分为假手术组、缺血对照组、L-NA治疗组,采用线栓法阻断大鼠大脑中动脉(MCAO)复制局灶性脑缺血模型,分别于缺血后2h、6h、12h给药治疗3d,迅速断头取脑,差速离心法提取缺血侧脑组织线粒休,迅速测定线粒体膜肿胀度及线粒体活力,测定线粒体总ATP酶、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,以及线粒休一氧化氮(NO)、丙二醛(MDA)含量:电镜观察缺血后皮层神经元超微结构的改变及L-NA对其影响。结果:在大鼠MCAO后线粒体膜肿胀度增加,线粒体活力下降,线粒体NO、MDA含量明显增加,线粒体总ATP酶、SOD、GSH-Px活性均明显下降:缺血后2h、6h、12h给予L-NA治疗3d与缺血对照组相比NO含量明显下降,缺血后12h治疗组线粒体膜肿胀度、线粒体活力、总ATP酶、SOD、GSH-Px活性均显著升高、MDA含量下降。电镜结果显示脑缺血后皮层神经元水肿,线粒体肿胀、嵴断裂、溶解、消失,且随缺血时间延长损伤加重;缺血后12h给予L-NA治疗能明显改善脑缺血引起的神经元水肿、线粒体肿胀和空泡化。结论:L-NA能明显抑制脑缺血后线粒体NO生成,在缺血早期给予L-NA对缺血性脑损伤无改善作用:缺血后期给予L-NA,能明显降低线粒体膜肿胀程度,改善线粒体能量供应,增强线粒体抗氧化作用及其活力,从而减轻脑缺血损伤。     

后肢远程缺血预处理对小鼠全脑缺血再灌注的保护作用及机理

目的:探讨肢端远程缺血预处理(limb remote ischemic preconditioning)对小鼠全脑缺血再灌注损伤的保护作用及其机制.方法:36只雄性C57小鼠,随机分为3组,即假手术组、对照组和LRPC预处理组,每组12只,假手术组分离双侧颈总动脉不结扎;对照组分离颈总动脉后结扎双侧颈总动脉,20 min后松线;LRPC组首先暴露双侧股动脉,然后结扎1 min,松开5 min,进行3个循环,最后结扎颈总动脉20min后松线.观察和比较各组小鼠海马神经元形态,MPO及炎性因子IL-1β、TNF-α和IL-10含量的变化.结果:再灌注24 h后,LRPC可明显抑制神经元形态的改变(P＜0.05),减少MPO、IL-1β和TNF-α含量,而增加抗炎因子IL-10的含量.结论:LRPC可显著减轻脑缺血再灌注损伤,可能与其降低海马组织TNF-o,IL-1β的含量,增加IL-10的含量有关.     

蛛网膜下腔出血对大鼠脑血流量和体感诱发电位的影响

目的：探讨蛛网膜下腔出血（ＳＡＨ）后脑血流量、体感诱发电位（ＳＥＰ）潜伏期的改变及其与一氧化氮（ＮＯ）的关系。方法：对假手术对照组和ＳＡＨ模型组大鼠检测２４ｈ局部脑血流量（ｒＣＢＦ）、ＳＥＰ潜伏期和血清及脑组织ＮＯ含量动态变化。结果：非开颅刺破Ｗｉｌｌｉｓ环的方法可成功地诱发ＳＡＨ。ＳＡＨ后ｒＣＢＦ立即降低,在２４ｈ内无恢复趋势。ＳＥＰ潜伏期于ＳＡＨ后１ｈ开始至２４ｈ明显延长。血清和脑组织ＮＯ含量     

Melatonin Ameliorates Cerebral Vasospasm After Experimental Subarachnoidal Haemorrhage Correcting Imbalance of Nitric Oxide Levels in Rats

In the present study, we investigated the in vivo effects of melatonin on SAH-induced cerebral vasospasm and oxidative stress, resulting from SAH in an experimental rat model. Twenty-eight rats (225–250 g) were divided into four groups equally: group 1; control, group 2; SAH, group 3; SAH plus placebo, and group 4; SAH plus melatonin. We used double haemorrhage method for SAH groups. Beginning 6 h after SAH, 20 mg/kg melatonin or equal volume of 0.9% saline was administered intraperitoneally twice daily for 5 days to groups 3 and 4, respectively. Melatonin or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificed at the end of this period. Brain sections at the level of the pons were examined by light microscopy. The lumen diameter and the vessel wall thickness of basilar artery were measured using a micrometer. The serum levels of cerebral vasodilator nitric oxide (NO), the brain levels of an intrinsic antioxidant superoxide dismutase (SOD) and a NO regulator arginase activities were measured. The brain levels of inducible nitric oxide (iNOS) and nitrotyrosine, a nitrosative stress parameter immunohistochemiacally determined. In conclusion, melatonin administration ameliorated cerebral vasospasm by increasing serum NO level and decreasing the brain the levels of arginase and oxidative stress. It is therefore possible that increased brain arginase activity after SAH may also have a significant role in the pathogenesis of vasospasm by limiting the availability of arginine for NO production.     

Expression of Nemo-Like Kinase (NLK) in the Brain in a Rat Experimental Subarachnoid Hemorrhage Model

This study aimed to investigate the expression of the Nemo-like kinase (NLK) in the brain after experimental subarachnoid hemorrhage (SAH) in rats. A total of 90 rats were randomly divided into six groups: control group, day 1, day 3, day 5, day 7, and day 14. Day 1, day 3, day 5, day 7, and day 14 groups were all SAH groups in which the rats were killed on days 1, 3, 5, 7, and 14, respectively. In SAH groups, autologous arterial blood was injected into cisterna magna once on day 0. Cross-sectional area of basilar artery was measured by H&E staining. Immunostaining and immunoblotting experiments were performed to detect the expression of NLK protein. Real-time polymerase chain reaction was used to analyze the presence and quantity of NLK mRNA. The level of oxidative stress in the artery was also measured. The basilar arteries exhibited vasospasm after SAH and became the most severe on day 3. The expressions of NLK protein and mRNA were decreased remarkably in SAH groups compared with the control group. The down-regulated expression of NLK was detected after SAH and the low ebb was on day 3, which was oppositely the peak time of oxidative stress. The expression of NLK was present mainly in the neurons in the brain and smooth muscle cells in the basilar artery. NLK is decreasingly expressed in an opposite time-course to the development of cerebral vasospasm (CVS) and SAH-induced brain injury in this rat experimental model of SAH and these findings might have important implications during the administration of specific NLK agonist to prevent or reduce CVS or neuronal apoptosis caused by SAH.     

Differential Regulation of Matrix-Metalloproteinases and Their Tissue Inhibitors in Patients with Aneurysmal Subarachnoid Hemorrhage

Background

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in vascular remodeling, (neuro)inflammation, blood-brain barrier breakdown and neuronal apoptosis. Proinflammatory mechanisms are suggested to play an important role during early brain injury and cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to analyze MMP-3, MMP-9, TIMP-1 and TIMP-3 in patients with SAH and their respective association with cerebral vasospasm (CVS).

Methods

Blood samples were collected in 20 SAH patients on days 1 to 7, 9, 11, 13 and 15 and 20 healthy age and gender matched volunteers. Serum MMPs and TIMPs were analyzed using enzyme-linked immunosorbent assay. Doppler sonographic CVS was defined as a mean blood flow velocity above 120 cm/sec in the middle cerebral artery. When discharged from hospital and at 6 month follow-up neurological outcome was evaluated using the Glasgow Outcome Score and the modified Rankin Scale.

Results

MMP-9 was higher in SAH patients compared to healthy controls (p<0.001). Patients with CVS (n = 11) had elevated MMP-9 serum levels compared to patients without CVS (n = 9, p<0.05). Higher MMP-9 was observed in the presence of cerebral ischemia associated with cerebral vasospasm (p<0.05). TIMP-1 was increased in patients with SAH on day 4 (p<0.05). There was an imbalance of the MMP-9/TIMP-1 ratio in favor of MMP-9 in SAH patients, in particular those with CVS (p<0.001). MMP-3 and TIMP-3 were significantly lower in SAH patients throughout day 4 and day 7, respectively (p<0.05). We did not find an association between MMP-, TIMP levels and neurological outcome after 6 months.

Conclusions

MMP-3 and -9 are differentially regulated in SAH patients with both enzymes showing peak levels correlating with the development of CVS. The inhibitors TIMP-1 and -3 were low during the acute phase after SAH and increased later on which might suggest a preponderance of pro-inflammatory mechanisms.     

Alteration of the cerebrovascular function of endothelin B receptor after subarachnoidal hemorrhage in the rat

The substantial role of endothelin-1 (ET-1) in the development of cerebral vasospasm (CVS) after subarachnoidal hemorrhage (SAH) has been demonstrated by numerous experimental and, recently, clinical investigations. Whether the expression or function of the ET(B) receptor is altered in CVS is still unclear, however. The aim of the present study was, therefore, to characterize the cerebroarterial ET(B) receptor function during CVS. Experimental CVS was induced by the rat double-hemorrhage model. Reduction of the cerebral blood flow (CBF) was confirmed by magnetic resonance perfusion-weighted imaging. Animals were sacrificed on days 3 (d3) and 5 (d5) after CVS induction. The basilar arteries (BA) were dissected, cut into ring segments, and prepared for measurement of isometric force in an organ bath. Concentration-effect curves (CECs) were constructed by cumulative application of ET-1, acetylcholine (Ach), or sarafotoxin S6c (S6c). Segments with (E+) endothelial function were used. CECs were compared by the maximum effect (E(max)), the pD2, and the shift calculated on the pD2 level. The pD2 is the negative decadic logarithm of the concentration producing the half maximal effect (-log10EC50). After SAH, the relative regional CBF in the d3 and d5 groups was reduced to 63% and 32%, respectively, of the CBF in controls. ET-1 induced a dose-dependent contraction of segments with and segments without CVS. In E+ segments, the E(max) for ET-1 was not significantly changed after SAH (mean values [ +/- SEM] of 104% +/- 4% for the control group, 106% +/- 4% for the d3 group, and 104% +/- 3% for the d5 group). The CECs, however, were significantly shifted to the left versus the control by factors of 2.4 in the d3 group and 3.6 in the d5 group. Relaxation by S6c was significantly reduced after SAH (E(max:) 73% +/- 11% in the control group, 21% +/- 13% in the d3 group, and 13% +/- 8% in the d5 group), whereas relaxation associated with Ach was not significantly changed (E(max): 45% +/- 7% in the control group, 56% +/- 6% in the d3 group, and 43% +/- 6% in the d5 group). Significant contraction by S6c was not observed in E+ and E - segments in any of the study groups. The present data indicate the loss of the ET(B) receptor-mediated relaxation of the cerebral arteries in cases of CVS, which is independent of the endothelial nitric oxide synthase level.     

Effect of ischemic preconditioning on cerebral blood flow after subsequent lethal ischemia in gerbils

Ischemic tolerance, the phenomenon where a sublethal ischemic preconditioning protects the brain against a subsequent lethal ischemia, has been widely studied. Studies have been done on cerebral blood flow levels prior to the lethal ischemia, but the hemodynamic pattern after global ischemia with ischemic preconditioning has not been reported. Sequential changes in regional cerebral blood flow (rCBF) in gerbil hippocampus after 5 min global ischemia with or without 2 min ischemic preconditioning were studied to determine if ischemic preconditioning affects rCBF. Four different treatments were given: (1) sham-operated, (2) 2 min ischemia, (3) non-preconditioned, and (4) preconditioned. Groups (1) and (2) (both groups n = 5) were given a 24-h recovery period and the rCBF was measured for baseline values. 24 h after sham-operation (3) and 2 min ischemia (4), gerbils were subjected to 5 min ischemia followed by 1 h, 6 h, 1-day or 7-day reperfusion periods (all groups n = 5). Although no regional difference was observed in the recovery pattern of rCBF, the values of rCBF were significantly higher in the preconditioned group throughout whole brain regions including hippocampus. These results indicate that ischemic preconditioning facilitated the recovery of rCBF after 5 min global ischemia. It needs further study to determine whether the protecting effects of preconditioning relate to the early recovery of rCBF or not. However, our results could be interpreted that the early recovery of rCBF may lead to benefits for cell survival in the CA1 neuron, probably facilitating other protecting mechanisms.     

锌对急性缺氧小鼠海马NOS和nNOS水平的影响

目的：观察锌对急性缺氧小鼠海马一氧化氮合酶（nitric oxide synthase,NOS）和神经元型一氧化氮合酶（neuronal NOS,nNOS）阳性神经元的影响,以探讨锌抗脑缺氧的作用机制。方法：复制小鼠急性缺氧模型,采用NADPH-d组织化学和nNOS免疫组织化学方法,研究给锌组和不给锌组急性缺氧小鼠海马各分区NOS和nNOS阳性神经元数量的变化。结果：给锌组比不给锌组小鼠缺氧耐受时间显著延长,差异有显著性（P〈0．05）;海马及其CA1区NOS和nNOS阳性神经元的数量明显减少,差异有显著性（P〈0．05）。结论：急性缺氧时锌通过减少海马NoS和nNOS水平而发挥其抗脑缺氧作用。     

Prevention and reversal of vasospasm and ultrastructural changes in basilar artery by continuous infusion of CGS 35066 following subarachnoid hemorrhage

Endothelin-1, a potent vasoconstrictive peptide, has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). The goal of this study was to evaluate the effect of continuous intravenous infusion of a highly selective endothelin-converting enzyme-1 inhibitor, CGS 35066, on the prevention and reversal of cerebral vasospasm following SAH. New Zealand white rabbits were subjected to SAH by injecting autologous arterial blood into the cisterna magna. Infusion of CGS 35066 at dosages of 1, 3, or 10 mg/kg/ day was initiated either 1 hr and 24 hrs later in the prevention and reversal protocols, respectively. Animals were sacrificed by perfusion-fixation 48 hrs after SAH induction. The cross-sectional areas of basilar arteries were measured using computer-assisted videomicroscopy. Ultrastructural changes in basilar arteries were determined using electron microscopy. CGS 35066 significantly prevented and reversed the arterial narrowing after SAH in all three groups. The mean cross-sectional areas of arteries from animals in both the prevention and reversal protocol groups that received 10 mg/kg/day of CGS 35066 did not differ significantly from those of the healthy controls. Histological studies of the basilar artery in the 10 mg/kg/day treatment group did not show pathomorphological changes, such as corrugation of the endothelium seen at 2 days after SAH induction or vacuole formation in the endothelial cells noted in the vehicle-treated SAH group. These findings suggest that CGS 35066 is a promising therapeutic agent for the prevention and reversal of cerebral vasospasm after SAH. It also prevents the pathological changes in vascular walls due to SAH.     

Effects of interrupted and uninterrupted occlusion of the basilar artery on cerebral blood flow, and on neurological and histological outcome in rats with subarachnoid hemorrhage.

Most neurosurgeons consider temporary vessel occlusion for aneurysmal clipping an effective technique that facilitates dissection between the aneurysm and the parent vessel. It is generally believed that repeated short periods of cerebral ischemia are safer for the brain than a single long episode. The aim of this study was to identify whether interrupted and uninterrupted vessel occlusion differs with regard to changes in brain tissue and cerebral hemodynamics after subarachnoid hemorrhage (SAH). Fifty Spraque Dawley rats (300-350 g) were placed under general anaesthesia and ventilated. The basilar artery was exposed through a transclival approach. Baseline local cerebral blood flow (LCBF) values was measured, and then the basilar artery was punctured, causing subarachnoid hemorrhage (SAH). Group I (n = 24) was subjected to 60 min of interrupted basilar artery occlusion, defined as 5 min of reperfusion after every 10 min of occlusion, group II (n = 26) 60 min of uninterrupted artery occlusion. Three days after completion of the experiment, each rat was neurologically evaluated and decapitated. Coronal brain slices were obtained and stained to assess infarct volume. Immediately after SAH, LCBF fell by 58% in group I, and by 52% in group II. In group I, each ischemic insult brought a similar reduction in LCBF, and after each release of the occlusion there was a rapid rise in flow. In group II, the LCBF values dropped initially and remained at low levels until the end of the study. The 2,3,5 triphenyltetrazolium chloride stained sections showed similar volumes of brainstem infarction in both groups (38.3 +/- 9.2 mm3 vs. 34.3 +/- 8.7 mm3, respectively; p > 0.05). The results suggest that there is no neuroprotective advantage to either interrupted or uninterrupted temporary blockage of blood flow during neurovascular procedures after SAH in the basilar artery region.     

Effect of total flavonoid in rabdosia rubescens on tolerant mice models under cerebral anoxia

ObjectiveTo study the protective effect of total flavonoid in rabdosia rubescens on BIT model by brain ischemic tolerance (hereinafter BIT) model of mice.MethodBIT model is used to block bilateral common carotid arteries and to copy BIT model of mice. After 10 min of transient ischemia for rats in preconditioning group, the mice in the nimodipine group and naoluotong capsule group were given the total flavonoid in rabdosia rubescens (300 mg/kg, 150 mg/kg, 75 mg/kg) for gavage, sham operation group, ischemia/reperfusion injury (hereinafter IRI) group and BIT group were fed with the same volume of 0.5% sodium carboxymethyl cellulose (CMC) once a day for 5 days. After administration for 1 h on day 5 (120 h), the rats in the other groups except for the sham operation group were treated with blood flow block for 30 min and reperfusion for 22 h. The serum NSE level were measured and the brain NO content and NOS activity changes was measured to observe the histopathological changes of brain tissue.ResultsBIT models of mice and in rats were both successfully replicated. The total flavonoid in rabdosia rubescens can decrease the mortality of mice, decrease serum NSE level, increase the content of NO and the activity of NOS in the brain tissue of mice, and improve the pathological damage of cortex and hippocampus of mice.ConclusionThe total flavonoid in rabdosia rubescens can stimulate an endogenous protective mechanism by inducing the release of low levels of cytokines NO and NOS, which reduces the release of serum NSE, relieves the brain tissue ischemia-reperfusion injury, and further improves the protection effect of ischemic preconditioning on brain injury. The damage of brain tissue ischemia and reperfusion, and further improve the ischemia Protective effect of preconditioning on brain injury.