Nylon filament coated with paraffin for intraluminal permanent middle cerebral artery occlusion in rats

A variety of intraluminal nylon filament has been used in rat middle cerebral artery occlusion (MCAO) models. However the lesion extent and its reproducibility vary among laboratories. The properties of nylon filament play a part of reasons for these variations. In the present study, we used paraffin-coated nylon filament for rat MCAO model, tested the effects and advanced improvement for making the rat MCAO. Forty male Sprague-Dawley (SD) rats were randomized into two groups, MCAO with traditional uncoated nylon filament (uMCAO) and MCAO with paraffin-coated nylon filament (cMCAO), three rats as normal group and sham group respectively. Assessment included mortality rates, model success rates, neurological deficit evaluation, and infarct volume. The study showed two rats died in uMCAO group, no rat died in cMCAO group within the 12 h. The model success rate of uMCAO was 100%, while the uMCAO group was 55% (n = 20, two died within 12 h, seven rats were excluded as the brain slices showed no TTC staining due to subarachanoid hemorrhage). Neurological evaluation demonstrated group cMCAO had more worse neurological outcomes than group uMCAO, and the difference was statistically signification (p < 0.05). TTC staining cMCAO group had significantly larger infarct volumes than uMCAO group, and also showed statistically significant difference (p < 0.05). The result demonstrated that the paraffin-coated nylon filament intraluminal occlusion provide better occlusion of middle cerebral artery than the uncoated nylon filament, improve the consistent of model, and raise the success rate to reduce the number of experimental animals. These positive results are much encouraging and interesting.     

L-丝氨酸对永久性大脑中动脉栓塞大鼠的神经保护作用

目的: 研究L-丝氨酸对大鼠永久性脑梗死的神经保护作用、治疗剂量及有效治疗时间窗,并探讨相关作用机制。方法: 制作大鼠永久性大脑中动脉栓塞(pMCAO)模型,腹腔注射L-丝氨酸,通过神经行为学评分、脑梗死体积测定和尼氏染色法,观察L-丝氨酸的治疗剂量效应(56 mg/kg、168 mg/kg和504 mg/kg治疗组)和治疗时间窗(1 h、3 h、6 h、12 h和24 h治疗组);并测定丝氨酸消旋酶抑制剂对L-丝氨酸疗效的影响。利用激光多普勒血流监测仪观察缺血区血供及L-丝氨酸对缺血区局部脑血流量的影响。结果: 与pMCAO组相比,L-丝氨酸于pMCAO后3 h使用,168 mg/kg和504 mg/kg两个剂量都能较好地降低神经行为学评分,减少脑梗死体积,抑制海马CA1区神经细胞的丢失。在治疗时间窗的研究中,L-丝氨酸在pMCAO后6 h内治疗具有明显的神经保护作用,12 h及以后使用,神经保护作用不明显。丝氨酸消旋酶抑制剂不改变L-丝氨酸的疗效。脑缺血30 min时注射L-丝氨酸可明显增加缺血区局部脑血流量,并且这一作用不受甘氨酸受体阻断剂士的宁的影响。结论: L-丝氨酸对永久性脑梗死具有神经保护作用,其机制可能部分与增加缺血区皮质的血供有关。     

急性缺血性脑梗死大鼠皮层神经蛋白聚糖的表达

目的： 研究神经蛋白聚糖（neurocan）在急性缺血性脑梗死大鼠皮层内的表达。方法: 用电凝法制成大鼠右侧大脑中动脉梗死模型，在1周、2周和4周不同时期，采用免疫组化、实时荧光定量RT-PCR和Western blotting技术检测梗死灶同侧和对侧的neurocan表达。结果: Neurocan和GFAP的双标结果提示neurocan阳性区域要大于GFAP阳性区域，neurocan阳性染色主要分布于胶质细胞及细胞间隙，4周组较1周组与2周组neurocan mRNA表达显著降低，差异显著（P<0.01），neurocan表达显著降低，差异显著（P<0.05），各组的neurocan C-末端糖蛋白无显著差异（P>0.05）。结论: Neurocan主要分布于脑梗死周围皮质的细胞间隙。脑梗死后neurocan表达升高，第1-2周是高峰期，4周下降至低水平，提示neurocan参与脑梗死后病理生理过程。     

大鼠大脑中动脉缺血后海马星形胶质细胞反应的研究

目的:观察大鼠大脑中动脉缺血后皮层损伤侧海马星形胶质细胞反应的变化。方法:采用大鼠大脑中动脉阻塞再灌流模型,应用免疫印迹和免疫组织化学方法测定脑缺血后3 d、7 d以及30 d皮层损伤侧海马胶质纤维酸性蛋白(GFAP)以及增殖细胞核抗原(PCNA)蛋白的表达,观察星形胶质细胞增殖的变化。结果: GFAP免疫组化结果显示,脑缺血后7d皮层损伤侧海马CA1、CA2区星形胶质细胞数量较假手术组增加且胞体增大;脑缺血后30 d皮层损伤侧海马CA1、CA2区呈胶质疤痕样改变。同时,免疫印迹法显示脑缺血后7 d皮层损伤侧海马GFAP表达增强;脑缺血后30 d皮层损伤侧海马GFAP表达增高更加明显。此外,免疫印迹法显示脑缺血后3 d皮层损伤侧海马PCNA蛋白表达水平升高;脑缺血后7 d PCNA蛋白表达水平达到峰值;脑缺血后30 d,PCNA蛋白表达水平降低,但仍高于假手术组。结论: 大鼠大脑中动脉缺血后可引起其皮层损伤侧海马星形胶质细胞过度反应和增殖。     

人参皂苷RH2对MCAO大鼠血管新生的调节

目的:探讨人参皂苷RH2(ginsenoside RH2,GS-RH2)对大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型大鼠血管新生的调节作用及潜在的作用机制。方法:取健康雄性SPF级大鼠随机分为假手术组、模型组(MCAO组)和实验组(GS-RH2组),每组18只。各组经相应处理后,观察并分析动物的一般生存状况及神经功能评分;并在干预的第1、3和7天测定微血管密度(microvessel density,MVD)、脑组织中丙二醛(malondialdehyde,MDA)的含量及超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的活性;同时采用Western blot检测脑组织中Kelch样环氧氯丙烷相关蛋白1(Kelch-like ECH-associated protein 1,Keap1)、核因子E2相关因子2(nuclear factor E2-related factor 2,Nrf2)及血红素加氧酶1(heme oxygenase-1,HO-1)的蛋白表达水平。结果:与假手术组相比,模型组大鼠出现明显的神经行为障碍,脑梗死体积显著增加,且神经功能评分显著升高(P0.05);与模型组相比,干预7 d之后,GS-RH2组动物神经行为症状得到明显改善,脑梗死体积显著减小,神经功能评分显著降低(P0.05)。微血管密度分析显示,随动物生存时间的延长,实验组大鼠MVD值呈升高的趋势,而模型组大鼠MVD值则呈下降趋势,且在第7天时,实验组MVD值显著高于模型组(P0.05)。与假手术组相比,各时间点模型组MDA的含量均升高,SOD和GSH-Px的活性均降低;与模型组相比,干预7 d之后,GS-RH2组MDA的含量降低,SOD和GSH-Px的活性升高(P0.05)。Western blot结果显示,与模型组相比,干预7 d之后,实验组Nrf2及HO-1蛋白表达显著增加,Keap1蛋白表达显著减少。结论:人参皂苷RH2可促进MCAO大鼠血管新生,其作用机制可能与激活Keap1/Nrf2信号通路、提高抗氧化酶的活性从而抑制氧化应激反应有关。     

比较线栓法和电凝法制作小鼠大脑中动脉栓塞模型

目的:目前制作脑缺血模型的的方法主要包括四血管栓塞法、线栓法、光化学法等,每种方法都各有利弊.为了制作一个适合细胞移植治疗缺血性脑损伤的动物模型,本实验比较了电凝法和线栓法制作的小鼠大脑中动脉栓塞模型.方法:本实验采用电凝法和线栓法建立小鼠大脑中动脉栓塞模型.氯化三苯基四氮唑染色确定缺血坏死区.行为学实验评价模型的效果.结果:电凝组缺血坏死区局限在小鼠大脑皮质,而线栓法小鼠缺血坏死区的位置不恒定,而且成活率非常低,不能满足进一步的实验需求.在角落实验与圆筒实验,电凝组与假手术组之间有明显的行为学差异.结论:电凝法可成功建立大脑中动脉栓塞模型,为细胞移植治疗缺血性脑损伤奠定基础.     

Effects of CD11b/18 monoclonal antibody on rats with permanent middle cerebral artery occlusion.

The progression of a lesion from ischemic injury to infarct, after the permanent occlusion of a middle cerebral artery, may be influenced by the influx of leukocytes into the ischemic territory. We aimed to evaluate the effectiveness of treating rats that had permanent middle cerebral artery occlusion with a single dose of an anti-CD11b/18 monoclonal antibody injected 1 hour after the arterial occlusion. To mimic the clinical situation of patients with ischemic strokes who may be treated within 1 hour of the ischemic event, the artery remained occluded. Forty-one adult Wistar rats had permanent middle cerebral artery occlusion, and one was subjected to a sham operation. One hour later, 22 rats received CD11b/18 monoclonal antibody and an additional 20 were injected either with a nonspecific antibody (n = 10) or a buffer solution (n = 10). Experiments were terminated at intervals ranging 12 to 96 hours after the arterial occlusion. Endpoints included neurological testing, daily evaluation of body weight, counts of white blood cells in the peripheral blood, measurement of the area of pallor in the ischemic hemisphere, counts of necrotic neurons, and counts of leukocytes sequestered in the ischemic hemisphere. In experiments terminated 12 hours after the arterial occlusion (n = 4), there were fewer necrotic neurons in the group treated with the CD11b/18 monoclonal antibody compared with the two controls (P < .05), but this difference was not reflected in the neurological scores. Numbers of necrotic neurons in experiments terminated > 12 hours later were not different among the three subgroups. White blood cell counts in peripheral blood were lower in animals with arterial occlusion injected with the monoclonal antibody CD11b/18 (P < .05); numbers of leukocytes sequestered in the ischemic hemisphere were not different in the three groups. Neither changes in body weight nor in the volume of the area of pallor were significantly different among the three groups.     

间质干细胞移植在大鼠缺血性脑卒中的实验研究

目的:探索间质干细胞移植在脑梗塞大鼠的脑内分化及促进神经功能的修复作用。方法:从健康人的肋骨骨髓中分离、纯化而获得的间质干细胞,经体外培养、扩增、鉴定的同时制造大脑中动脉皮层梗塞的实验动物模型;并且,在梗塞后10 d移植所鉴定的间质干细胞经免疫组化验证间质干细胞的脑内成活、及神经性分化后,在第2周和第6周进行神经功能评分。结果:间质干细胞在梗塞灶周边向神经元和神经胶质细胞的方向分化;移植的神经功能评分,修复作用与对照组有显著差异。结论:人间质干细胞为脑梗塞治疗提供了新的思路。     

Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion

The usefulness of the administration of hyperbaric oxygen (HBO) in the treatment of acute focal cerebral ischemia remains debatable. A significant association exists between focal cerebral injury and an excessive release of extracellular dopamine (DA). In vivo microdialysis was used in the present study to examine the effect of HBO on DA release in the striatum during ischemia and reperfusion in rats. The histological changes occurring were also evaluated. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery (MCA) using a surgically placed intraluminal filament. Control rats (n=8) were subjected to 1 h of ischemia, whilst the study rats (n=8) were in addition treated with HBO (2.8 atmospheres of absolute pressure 100% O₂) during ischemia. Both groups were returned to breathing room air at normal pressure during reperfusion. Microdialysis samples were continuously collected at 15 min intervals at 2 μl·min^–1. The [mean (SE)] increase in release of striatal DA attained significance after 30 min of occlusion of MCA [170 (24)%], and continued to increase [268 (26)% at 45 min] reaching a peak level at 60 min [672 (59)%] before returning to the baseline level during the late reperfusion phase. There was no significant change in the level of DA in HBO treated rats during the period of ischemia. A significant reduction in edema and neuronal shrinkage were observed by histological examination in HBO treated rats when compared to the control rats. The results showed that HBO, when administered during ischemia, offered significant neuroprotection in our experimental model of transient focal cerebral ischemia in the rat. The mechanism seems to imply, at least in part, a reduced level of DA. Electronic Publication     

Comparison of perfusion MRI by flow-sensitive alternating inversion recovery and dynamic susceptibility contrast in rats with permanent middle cerebral artery occlusion

We compared cerebral blood flow (CBF) parameters obtained by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with those obtained by flow-sensitive alternating inversion recovery (FAIR) in brain regions with different perfusion levels in rats with permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed in 19 rats. T2-weighted MRI, FAIR and DSC-MRI were performed within 48 h after occlusion. CBF parameters were analyzed in regions of interest with either prolonged or less prolonged mean transit time (MTT). Ratios of ipsi- vs contralateral CBF values were calculated and tested for correlation and differences between FAIR and DSC-MRI. FAIR-aCBF ratios correlated significantly with DSC-rCBF ratios. The mean FAIR-aCBF ratio was significantly lower than mean DSC-rCBF ratio in the area with prolonged MTT. In the area with less prolonged MTT, the mean FAIR-aCBF ratio and mean DSC-rCBF values did not differ significantly. We conclude that FAIR correlates with DSC-MRI if perfusion is preserved. FAIR provides lower CBF values than DSC-MRI if perfusion is reduced and MTT is prolonged. This probable underestimation of perfusion may be caused by transit delays. Care should be taken when quantifying CBF with FAIR and when comparing the results of FAIR- and DSC-MRI in areas with hypoperfusion.     

Morphology of tissue damage caused by permanent occlusion of middle cerebral artery in mice.

In two series of experimental occlusion of the middle cerebral artery (MCA) in mice, the time course and the evolution of morphological changes were followed. Both series comprised control animals used in experiments for the screening of neuroprotective and therapeutic effects after focal ischemia. In both series the left MCA was permanently occluded and the animals were sacrificed by perfusion fixation at certain time intervals following occlusion. In the first series the follow up was continued until the 30th day after ischemia. In the second, the observation period was extended to two months. The general question was addressed, whether or not such experimental settings can contribute to the understanding of cellular (necrosis vs apoptosis) and tissue (resorption vs scar) reaction. In the two series the technical procedures were only slightly different. Nevertheless, the development of morphological sequelae was at variance. Differences in tissue reaction in both sets revealed features that were rarely observed in previous protocols. In the first series, infarct areas were different in size, often a central part near the meninges was preserved and gave rise to a prominent mesenchymal reaction. In the second series, infarcts had almost constant size and mesenchymal reaction changes were minimal. The end product in both series, however, was a shallow groove much smaller than the primary well-demarcated defect. We conclude that minor technical variations of MCA occlusion in the mouse demonstrate the variability of occlusion sequelae due to collateral irrigation known from human cerebral pathology. On the cellular level, neuronal death is obviously completed during the first 24 hours in the infarct core. Thus, the mechanism of neuronal damage can only be best observed by morphology at the transition between completed territorial necrosis and unchanged tissue: shrunken neuronal perikarya develop into pycnotic nuclei, that may be interpreted as apoptosis. A second area of partial damage is marked by gliosis. Astrocytic reaction extended far beyond the infarct border, even to the contralateral hemisphere and could represent a component of size compensation.     

Ketamine-induced rotational asymmetry in evaluation of motor disturbances in rats with middle cerebral artery occlusion

Intraperitoneal injection of ketamine in subanesthetic doses to Wistar rats with unilateral occlusion of the middle cerebral artery caused ipsilateral rotation (2-10 rpm), which was recorded in an automatic rotameter. The optimal dose of ketamine was 50 mg/kg. The animals were examined in an automatic rotameter for 40 min. Motor asymmetry persisted for no less than 2 months after surgery. According to the neurological test (Menzies scale) motor asymmetry in animals with focal brain ischemia persisted for no more than 30 days. The degree of ketamine-induced motor asymmetry in intact rats was 0.10±0.03 rpm.     

Ischemic penumbra in a model of reversible middle cerebral artery occlusion in the rat

Summary It has become increasingly clear that a stroke lesion usually consists of a densely ischemic focus and of perifocal areas with better upheld flow rates. At least in rats and cats, some of these perifocal (penumbral) areas subsequently become recruited in the infarction process. The mechanisms may involve an aberrant cellular calcium metabolism and enhanced production of free radicals. In general, though, the metabolic perturbation in the penumbra requires better characterization. The objective of this article was to define flow distribution in a rat model of reversible middle cerebral artery (MCA) occlusion, so as to allow delineation of the metabolic aberrations responsible for the subsequent infarction. We modified the intraluminal filament occlusion model recently developed by Koizumi et al. (1986), and described in more detail by Nagasawa and Kogure (1989), adopting it for use in both spontaneously breathing and artificially ventilated rats. Successful occlusion of the MCA (achieved in about 9/10 rats) was judged by unilateral EEG depression in ventilated rats, and neurological deficits, such as circling, in spontaneously breathing ones. CBF in the ipsilateral hemisphere was reduced to nearly constant values after 20, 60, and 120 min of occlusion, flow rates in the focus being about 10% and in the perifocal ipsilateral areas about 15–20% of control (contralateral side). When the filament was left in place (permanent occlusion) 2,3,5-triphenyl tetrazolium chloride (TTC) staining and histopathology after 24 h showed a massive infarct on the occluded side, extending from caudoputamen and overlaying cortex to the occipital striate cortex. Animals recirculated after 60 min of MCA occlusion, and allowed to survive 7 days for histopathology, showed infarction of the caudoputamen (lateral part or whole nucleus) in 5/6 animals and selective neuronal necrosis in one animal. The neocortex showed either infarcts, selective neuronal necrosis, or no damage. There was some overlap between neocortical areas which were infarcted and those which were salvaged by reperfusion. In general, though, both the CBF data and the recovery studies with a histopathological endpoint define large parts of the neocortex as perifocal (penumbral) areas which lend themselves to studies of metabolic events leading to infarction.     

Acupuncture prevents cognitive deficits and oxidative stress in cerebral multi-infarction rats

The aim of this study is to investigate the effects of acupuncture on cognitive deficits and oxidative stress in cerebral multi-infarction rats. The results showed that acupunctural treatment attenuated memory impairment induced by cerebral multi-infarction, as evaluated by shortened escape latency and increased swimming time of rats with memory impairment in the target quadrant. The data additionally suggested that acupunctural treatment ameliorated oxidative injuries induced by cerebral multi-infarction by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus. Further investigation by in situ hybridization and immunohistochemistry revealed that acupunctural treatment significantly increased the expression of CuZnSOD mRNA and protein in the hippocampus of the impaired rats. The findings demonstrate that acupuncture can exert beneficial effects on spatial memory and antioxidant status of cerebral multi-infarction rats.     

Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats

Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague–Dawley rats were ovariectomized and divided into placebo and estradiol-treated groups. Two weeks later, halothane-anesthetized rats underwent middle cerebral artery (MCA) occlusion by interparenchymal stereotactic injection of the potent vasoconstrictor endothelin 1 (180 pmoles/2 μl) near the middle cerebral artery. Laser-Doppler flowmetry (LDF) revealed similar reductions in cerebral blood flow in both groups. Animals were behaviorally evaluated before, and 2 days after, stroke induction, and infarct size was evaluated. In agreement with other models, estrogen treatment significantly reduced infarct size evaluated by both TTC and Fluoro-Jade staining and behavioral deficits associated with stroke. Stroke size was significantly correlated with LDF in both groups, suggesting that cranial perfusion measures can enhance success in this model.     

Nuclear translocation of endonuclease G in degenerating neurons after permanent middle cerebral artery occlusion in mice

Endonuclease G (EndoG) is a mitochondrial enzyme, known to be involved in caspase-independent cell death following translocation to the cellular nucleus. Nuclear translocation of EndoG has been observed in the ischemic area following transient occlusion of the middle cerebral artery (MCA) in mice, but not after permanent MCA occlusion. In this study we investigated the cellular and temporal expression of EndoG in infarcted cortex during the first 24 h after permanent MCA occlusion in mice, using immunohistochemistry, quantitative rt-PCR and cell specific immunoflourescence markers. EndoG translocated from the cytoplasm to the nucleus as early as 4 h and with a significant increase in the number of EndoG positive nuclei at 12 and 24 h after MCA occlusion. Nuclear translocation of EndoG was observed in degenerating NeuN positive neurons that were evenly distributed throughout the developing infarct. Translocation of EndoG was supported by unaltered EndoG mRNA levels. EndoG was neither expressed in GFAP positive astrocytes nor in CD11b positive microglia/macrophages. In contrast, CD11b positive microglia, but not infiltrating CD11b positive bone marrow-derived macrophages, were shown to express activated caspase-3. The translocation of EndoG to the nucleus of neurons in the infarct implicates EndoG in ischemic neuronal degeneration after permanent MCA occlusion in mice. Increased knowledge about EndoG involvement in ischemic neuronal cell death in mice might offer a promise to control processes involved in neuronal cell death pathways in stroke.     

Electrophysiological transcortical diaschisis after middle cerebral artery occlusion (MCAO) in rats

Remote changes in brain function following stroke are called diaschisis. These remote effects may contribute to the neurological deficit following brain infarction; in addition they may lead to post-stroke epilepsy and affect functional recovery. In the present study we addressed the question of whether an increase in excitability can be observed contralateral to middle cerebral artery (MCA) infarction. Permanent occlusion of the middle cerebral artery (MCAO) was induced experimentally in rats with an intraluminal silicon-coated filament. Seven days later, brain excitability was tested with extracellulare recording techniques in neocortical coronal brain slices using a paired-pulse stimulus protocol. In rats with MCAO, excitability was increased in the neocortex contralateral to the infarction compared with the control group. These alterations extended through wide parts of the contralateral neocortex. The study demonstrates that MCAO causes transcallosal electrophysiological diaschisis. Together with results obtained previously with photothrombotic cortical lesions, it can be concluded that these remote effects are not due to characteristics of the individual lesion model, but are common consequences of brain lesions.     

大脑中动脉阻塞后脑组织病变过程及MDA含量变化

在大鼠中用热凝造成大脑中动脉阻塞而致脑局灶性缺血。电镜观察发现,在缺血2min后,神经细胞粗面内质网与线粒体即出现改变。光镜检查,缺氧10min后才出现神经细胞缺血改变;梗死灶周边微血管体积密度在缺血24h后即明显升高。肉眼检查,于缺血3h后可见梗死灶。在缺血2min后,脑组织内丙二醛(MOA)即升高,说明在缺血缺氧的早期,脂质过氧化作用加强。表明自由基在缺血性脑损伤早期即起重要作用。     

虫草素对大脑中动脉局灶性脑缺血模型大鼠氧化应激和脑损伤的影响

目的　研究虫草素对大脑中动脉局灶性脑缺血模型大鼠氧化应激指标和脑组织Caspase-3和p53表达的影响。 方法　首先，给药组大鼠每天分别腹腔注射虫草素5、10、20 mg/kg，连续10 d；然后，采用改良Zea Longa线栓法制备大脑中动脉闭塞（middle cerebral artery occlusion，MCAO）模型；造模24 h后，盲法进行神经功能评分，称重法检测脑含水量，HE染色观察脑组织病理损伤，Tunnel染色检测脑细胞凋亡，RT-PCR检测Bcl-2、Bax、Caspase-3和p53 mRNA表达，Western blotting检测Bcl-2、Bax、Caspase-3和p53蛋白表达，试剂盒检测SOD，MDA，GSH水平。 结果　给药组与MCAO组相比，神经功能评分显著降低，脑含水量显著减少，细胞损伤减轻，细胞凋亡率显著减少，Bax mRNA及蛋白表达显著下调，Bcl-2 mRNA及蛋白表达显著上调，MDA含量显著下降，SOD和GSH含量显著上升，Caspase-3和p53 mRNA及蛋白表达显著下调，且这些效果随着虫草素给药量的增加更加显著。 结论　虫草素能够缓解大脑中动脉局灶性脑缺血引起的神经功能障碍和降低脑缺血引起的脑含水量升高，并能抑制大脑中动脉局灶性脑缺血模型大鼠氧化应激和细胞凋亡，从而减缓大脑中动脉局灶性脑缺血造成的损伤。