Neuroprotective effect of tyrosol on transient focal cerebral ischemia in rats

Tyrosol (2-(4-hydroxyphenyl)ethanol) is a well-known phenolic compound with antioxidant properties that is present in wine, olive oil, and other plant-derived products. The purpose of this study was to determine the neuroprotective effect of tyrosol in a stroke animal model. By using the transient middle cerebral artery occlusion rat model (2 h of occlusion, 22 h of reperfusion), we investigated the effects of tyrosol on infarct volume and sensory motor function deficit by performing 2,3,5-triphenyltetrazolium chloride staining and behavior tests after ischemia. Tyrosol showed a dose-dependent neuroprotective effect that peaked at 64.9% in rats treated with 30 mg/kg of tyrosol. In rotarod, beam balance, and foot fault tests, tyrosol exhibited protective effects against the sensory motor dysfunction. In conclusion, our results suggest that tyrosol is an appropriate candidate to be used in stroke therapy.     

Altered expression of sodium transporters in ischemic penumbra after focal cerebral ischemia in rats

This study was aimed to examine whether the changes of protein expression of sodium transporters in the ischemic penumbra are associated with the pathogenesis of ischemia-induced brain edema and/or brain cell injury. An experimental model of cerebral ischemia was made by permanent middle cerebral artery occlusion (pMCAO) in rats and the changes of protein expression of sodium transporters in the ischemic penumbra were examined by immunoblotting. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 3 and 6h after pMCAO. Immunoblotting analyses revealed significantly increased expressions of electrogenic NBC (241 +/- 11% at 3 h and 154 +/- 9% at 6 h, P < 0.05) and NHE1 (144 +/- 3% at 3 h and 170 +/- 9% at 6 h, P < 0.05), compared with sham-operated controls. In contrast, Na-K-ATPase expression (78 +/- 6% at 3 h and 85 +/- 3% at 6 h, P < 0.05) was significantly decreased. The expression of NCX1 was unchanged at 3 h, but was significantly increased at 6 h (141 +/- 3%, P < 0.05). In addition, the expressions of neuronal (NeuN) and astroglial cell (GFAP) proteins were decreased, whereas the expression of oligodendrocyte protein (CNPase) was unchanged. Taken together, the selectively increased expressions of NHE1, electrogenic NBC, and NCX1 and decreased expression of Na-K-ATPase in the ischemic penumbra are likely to contribute to the secondary brain cell damages presumably through intracellular Na(+) accumulation, cell swelling, and intracellular Ca(2+) overload.     

Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats

Lidocaine is a local anesthetic and antiarrhythmic agent. Although clinical and experimental studies have shown that an antiarrhythmic dose of lidocaine can protect the brain from ischemic damage, the underlying mechanisms are unknown. In the present study, we examined whether lidocaine inhibits neuronal apoptosis in the penumbra in a rat model of transient focal cerebral ischemia. Male Wistar rats underwent a 90-min temporary occlusion of middle cerebral artery. Lidocaine was given as an i.v. bolus (1.5 mg/kg) followed by an i.v. infusion (2 mg/kg/h) for 180 min, starting 30 min before ischemia. Rats were killed and brain samples were collected at 4 and 24 h after ischemia. Apoptotic changes were evaluated by immunohistochemistry for cytochrome c release and caspase-3 activation and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) for DNA fragmentation. Cytochrome c release and caspase-3 activation were detected at 4 and 24 h after ischemia and DNA fragmentation was detected at 24 h. Double-labeling with NeuN, a neuronal marker, demonstrated that cytochrome c, caspase-3, and TUNEL were confined to neurons. Lidocaine reduced cytochrome c release and caspase-3 activation in the penumbra at 4 h and diminished DNA fragmentation in the penumbra at 24 h. Lidocaine treatment improved early electrophysiological recovery and reduced the size of the cortical infarct at 24 h, but had no significant effect on cerebral blood flow in either the penumbra or core during ischemia. These findings suggest that lidocaine attenuates apoptosis in the penumbra after transient focal cerebral ischemia. The infarct-reducing effects of lidocaine may be due, in part, to the inhibition of apoptotic cell death in the penumbra.     

大鼠局灶性短暂脑缺血后前脑室下带的神经发生

目的：观察大鼠短暂性局灶性脑缺血后前脑室下带(SVZ)神经发生的增殖规律。方法：将SD大鼠随机分为正常对照组、假手术组和缺血实验组,缺血实验组再分为缺血后1、4、7、10、14d组。线栓法制作局灶性脑缺血模型;BrdU标记S期细胞并用免疫组织化学方法检测含BrdU的阳性细胞;测量SVZ区域BrdU阳性细胞核的总面积。结果：在缺血侧,缺血后4d BrdU阳性细胞核的总面积明显增加,7d时达到峰值,随后开始下降,在14d时明显下降,但仍高于正常对照组;在缺血对侧,该区域也表现出同样的表达规律,在缺血后10d达到峰值,但增幅较小。结论：短暂性局灶性脑缺血可促进前脑室下带的神经发生,提示成年脑有潜在的自我修复能力。     

Inflammation and the neurovascular unit in the setting of focal cerebral ischemia

Responses to focal cerebral ischemia by neurons and adjacent microvessels are rapid, simultaneous, and topographically related. Recent observations indicate the simultaneous appearance of proteases by components of nearby microvessels that are also expressed by neurons in the ischemic territory, implying that the events could be coordinated. The structural relationship of neurons to their microvascular supply, the direct functional participation of glial cells, and the observation of a highly ordered microvessel-neuron response to ischemia suggest that these elements are arranged in and behave in a unitary fashion, the neurovascular unit. Their roles as a unit in the stimulation of cellular inflammation and the generation of inflammatory mediators during focal cerebral ischemia have not been explored yet. However, components of the neurovascular unit both generate and respond to these influences under the conditions of ischemia. Here we briefly explore the potential inter-relationships of the components of the neurovascular unit with respect to their potential roles in ischemia-induced inflammatory responses.     

Differential production of MCP-1 and cytokine-induced neutrophil chemoattractant in the ischemic brain after transient focal ischemia in rats.

Chemokines have been shown to play an important role in leukocyte infiltration into ischemic lesions. Recently, the increased expression of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC) was observed in experimental stroke models where infiltrated leukocytes were supposed to induce tissue injury, however, the protein level and time course of these chemokines have not been fully elucidated. Therefore, we analyzed the time-dependent production of MCP-1 and CINC in the rat brain after transient middle cerebral artery occlusion (MCAO) by means of specific enzyme-linked immunosorbent assay systems. The MCP-1 levels in the ipsilateral hemispheres increased from 6 h, peaked at 2 days, and thereafter gradually decreased. The peak MCP-1 concentration was 89.2+/-28.2 ng/g tissue wet weight (mean +/- SEM, n = 5, 49.3-fold greater than the contralateral value at the same time, P < 0.05), which is supposed to be high enough to exert its biological effects. In contrast, the maximum CINC concentration that corresponded to 2.9+/-0.7 ng/g tissue wet weight (mean +/- SEM, n = 5, 55.0-fold greater than the contralateral value at the same time, P < 0.05), was observed at 6 h. In addition, we confirmed the temporal profile of leukocyte subtypes that infiltrated into the ischemic brain, thus, neutrophil infiltration occurred at early stages (1-3 days), followed by massive infiltration of macrophages at later stages (2-7 days). These studies suggest that MCP-1 in cerebral ischemia actually plays a significant role in the migration of macrophages into the lesion and that the differential temporal production of these chemokines contributes to the regulation of infiltrated leukocyte subtypes.     

不同鼠龄大鼠心肌组织中钙敏感受体的表达及与缺氧-再灌注损伤的关系

目的：观察不同鼠龄大鼠心肌组织钙敏感受体（CaSR）的表达规律及与心肌缺氧-再灌注损伤的关系。方法： 采用RT-PCR技术，检测不同情况下心肌组织CaSR的表达差异；Lagendorff离体心脏灌流的方法复制心脏缺氧-再灌注模型；用透射电镜观察心肌超微结构的变化。结果：大鼠出生后，心肌组织中CaSR的表达逐渐升高，1个月时达到高峰，2、3个月保持在出生水平，此后上升并维持在较高水平。大鼠心肌缺氧40 min及再灌注1 h、2 h心肌组织CaSR的mRNA表达升高，再灌注3 h、4 h后降低；同时随再灌注时间延长，心肌超微结构损伤愈严重结论：大鼠心肌组织存在钙敏感受体，其表达与月龄有一定关系，并可能参与心肌缺氧-再灌注损伤的发生。     

CEPO经Mashl信号促进大鼠局部脑缺血后纹状体内神经发生

为检测氨甲酰化促红细胞叶三成素(CEPO)在大鼠脑缺血后发生过程中的作用及其相关信号通路,本实验将成年大鼠大脑中动脉栓塞(MCAO)后立即尾静脉给予CEPO(50μg/kg).结果显示:CEPO可显著降低大鼠MCAO后3 d梗塞面积,增加缺血侧神经于细胞增殖、促进神经干细胞分化成为神经元.CEPO的促神经发生效应与缺血侧纹状体内前神经元bHLH转录因子Mash1的表达上调密切相关.本结果提示CEPO对脑缺血具有神经保护作用,Mash1信号在缺血侧纹状体内可能介导CEPO增强的神经发生和神经元分化效应.     

Down-regulated Na+/K+-ATPase activity in ischemic penumbra after focal cerebral ischemia/reperfusion in rats

This study was aimed to examine whether the Na⁺/K⁺ adenosine triphosphatase (Na⁺/K⁺-ATPase) activity in ischemic penumbra is associated with the pathogenesis of ischemia/reperfusion-induced brain injury. An experimental model of cerebral ischemia/reperfusion was made by transient middle cerebral artery occlusion (tMCAO) in rats and the changes of Na⁺/K⁺-ATPase activity in the ischemic penumbra was examined by Enzyme Assay Kit. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 6 h, 24 h, 48 h, 3 d and 7 d after tMCAO. Enzyme Assay analyses revealed the activity of Na⁺/K⁺-ATPase was decreased in the ischemic penumbra of model rats after focal cerebral ischemia/reperfusion compared with sham-operated rats, and reduced to its minimum at 48 h, while the infarct volume was enlarged gradually. In addition, accompanied by increased brain water content, apoptosis-related bcl-2 and Bax proteins, apoptotic index and neurologic deficits Longa scores, but fluctuated the ratio of bcl-2/Bax. Correlation analysis showed that the infarct volume, apoptotic index, neurologic deficits Longa scores and brain water content were negatively related with Na⁺/K⁺-ATPase activity, while the ratio of bcl-2/Bax was positively related with Na⁺/K⁺-ATPase activity. Our results suggest that down-regulated Na⁺/K⁺-ATPase activity in ischemic penumbra might be involved in the pathogenesis of cerebral ischemia/reperfusion injury presumably through the imbalance ratio of bcl-2/Bax and neuronal apoptosis, and identify novel target for neuroprotective therapeutic intervention in cerebral ischemic disease.     

小胶质细胞在大鼠暂时性局灶脑缺血再灌注后脑损伤区活化反应的初步研究

目的:探讨暂时性局灶脑缺血后小胶质细胞的反应规律,进一步探讨小胶质细胞在脑缺血损伤中的作用。方法:采用线栓法建立大鼠大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)再灌注模型,应用组织学、免疫组化染色及免疫荧光双标技术,观察大脑中动脉阻塞30 min,再灌注0.5、3、6 h以及1、3、7、14 d和28 d后脑组织的损伤情况,小胶质细胞的形态学和数量变化。结果:组织学观察结果显示:MACO30 min再灌注0.5 h后,梗死区出现神经元肿胀,脑水肿;再灌注3 h和6 h,脑水肿加重,部分神经元出现核固缩,对侧脑组织也出现水肿。脑水肿和神经元固缩在再灌注1 d时最重。再灌注3 d开始,脑水肿程度逐渐减弱,缺血区浸润的小胶质细胞增多。再灌注7 d时,缺血灶小胶质细胞浸润最明显,伴胶质结节形成,再灌注14 d,胶质瘢痕逐渐减小。再灌注28 d,大多数动物梗死区仅存少量小胶质细胞,个别未能修复的坏死灶液化并形成囊腔。免疫组化和免疫荧光双标记结果显示:假手术组小胶质细胞的胞体小,突起细长柔和。脑缺血30 min再灌注0.5 h可见小胶质细胞的体积增大,突起少而短。缺血再灌注6 h,小胶质细胞的胞体增大,突起减少或消失。再灌注1 d和3 d,小胶质细胞的数量明显多于假手术组(P0.05)。再灌注7 d,细胞数量增加达到高峰。再灌注14 d以后,小胶质细胞的数量进一步减少,再灌注28 d后小胶质细胞的数量少于再灌注7 d,但仍多于假手术组和缺血再灌注3 d(P0.05)。结论:暂时性局灶脑缺血能够引起小胶质细胞活化和增生,经历损伤性、反应性、效应性和恢复性变化四个阶段。小胶质细胞在脑缺血损伤组织的清除和损伤修复等方面发挥重要作用。     

大鼠局灶性脑缺血/再灌注后缺血脑区缓激肽含量的变化

目的研究大鼠局灶性脑缺血/再灌注后缺血脑区缓激肽含量的变化。方法用线栓法制作SD大鼠大脑中动脉阻塞的脑缺血/再灌注动物模型,用免疫细胞化学法结合图像分析技术,检测缺血脑区缓激肽样免疫反应阳性物的平均光密度(A)值作为缓激肽的相对含量,比较局灶性脑缺血3h组、假手术对照组、正常对照组和再灌注30min、2h、4h、16h组缓激肽的相对含量。结果缺血脑区缓激肽样免疫反应阳性物的A值于脑缺血3h/再灌注2h后明显增高(P<0.05),随后下降至增高前水平。结论大鼠局灶性脑缺血/再灌注后,缺血脑区缓激肽含量于再灌注2h后明显增高,其可能在脑缺血后脑水肿的发生中起着重要作用。     

黄芩茎叶黄酮对慢性脑缺血大鼠脑内NMDA受体和VEGF表达的影响

目的: 探讨黄芩茎叶黄酮(SSF)对慢性永久性脑缺血大鼠脑内N-甲基-D-天门冬氨酸受体(NMDAR)和血管内皮生长因子(VEGF)表达的影响。方法: 雌性Sprague-Dawley(SD)大鼠双侧颈总动脉结扎2个月制备慢性脑缺血记忆障碍模型,通过RT-PCR测定海马细胞中NMDAR mRNA和皮层细胞中VEGF mRNA的含量。结果: 与假手术组相比,模型组大鼠海马细胞中NMDAR1 mRNA、NMDAR2A mRNA和NMDAR2B mRNA 的含量显著增加(P<0.01),皮层细胞中VEGF mRNA的含量明显增加(P<0.01);而 SSF 17.5 mg·kg^-1·d^-1、35 mg·kg^-1·d^-1和70 mg·kg^-1·d^-1灌胃给药38 d,能明显降低海马细胞中NMDAR1 mRNA、NMDAR2A mRNA和NMDAR2B mRNA 的含量,显著增加皮层细胞中VEGF mRNA的含量。结论: SSF 能够明显降低脑缺血大鼠海马细胞中NMDAR 的表达,明显增加皮层细胞中VEGF 的表达,提示SSF可能通过影响NMDAR和VEGF的生成发挥神经保护作用。     

依达拉奉联合灯盏花素对脑缺血大鼠大脑皮质MCP-1的影响

目的　观察大鼠脑缺血（MCAO）后大脑皮质MCP-1的表达变化以及用依达拉奉联合灯盏花素干预后对MCP-1表达的影响。 方法　复制大鼠大脑中动脉闭塞（MCAO）模型,应用RT-PCR、Western blot和免疫荧光技术检测大鼠MCAO及药物干预后MCP-1的表达变化。 结果　RT-PCR显示大鼠MCAO后大脑皮质MCP-1 mRNA的表达比对照组显著上升（P<0.05）,12 h达高峰,与1 d、3 d及1周组比有显著差异（P<0.05）;给予两种药物联合处理后,mRNA表达显著降低,与对照组及单独用药组相比均有显著差异（P<0.05）。 Western blot显示MCAO 1 d、3 d、1周大脑皮质MCP-1蛋白的表达显著增强,与对照组比有显著差异（P<0.05）;两种药物联合处理后,MCAO大鼠大脑皮质MCP-1蛋白表达明显减少,与对照组及单独用药相比均有显著差异（P<0.05）。免疫荧光染色显示MCAO大鼠缺血半暗带有大量激活小胶质细胞,一部分与MCP-1免疫阳性细胞有共表达,其中MCAO后1周组最明显。 结论　大鼠局灶性脑缺血（MCAO）后,依达拉奉联合灯盏花素治疗能有效减少大脑皮质MCP-1的表达,效果优于两种药物单独使用。     

Cilostazol attenuates ischemic brain injury and enhances neurogenesis in the subventricular zone of adult mice after transient focal cerebral ischemia

Evidence suggests that neurogenesis occurs in the adult mammalian brain, and that various stimuli, for example, ischemia/hypoxia, enhance the generation of neural progenitor cells in the subventricular zone (SVZ) and their migration into the olfactory bulb. In a mouse stroke model, focal ischemia results in activation of neural progenitor cells followed by their migration into the ischemic lesion. The present study assessed the in vivo effects of cilostazol, a type 3 phosphodiesterase inhibitor known to activate the cAMP-responsive element binding protein (CREB) signaling, on neurogenesis in the ipsilateral SVZ and peri-infarct area in a mouse model of transient middle cerebral artery occlusion. Mice were divided into sham operated (n=12), vehicle- (n=18) and cilostazol-treated (n=18) groups. Sections stained for 5-bromodeoxyuridine (BrdU) and several neuronal and a glial markers were analyzed at post-ischemia days 1, 3 and 7. Cilostazol reduced brain ischemic volume (P<0.05) and induced earlier recovery of neurologic deficit (P<0.05). Cilostazol significantly increased the density of BrdU-positive newly-formed cells in the SVZ compared with the vehicle group without ischemia. Increased density of doublecortin (DCX)-positive and BrdU/DCX-double positive neural progenitor cells was noted in the ipsilateral SVZ and peri-infarct area at 3 and 7 days after focal ischemia compared with the vehicle group (P<0.05). Cilostazol increased DCX-positive phosphorylated CREB (pCREB)-expressing neural progenitor cells, and increased brain derived neurotrophic factor (BDNF)-expressing astrocytes in the ipsilateral SVZ and peri-infarct area. The results indicated that cilostazol enhanced neural progenitor cell generation in both ipsilateral SVZ and peri-infarct area through CREB-mediated signaling pathway after focal ischemia.     

局灶脑缺血再灌注成年模型大鼠大脑髓鞘相关蛋白的基因表达

背景：髓鞘蛋白是少突胶质细胞的主要成分,研究脑缺血再灌注后大脑髓鞘相关蛋白基因表达的变化有助于探讨少突胶质前体细胞在缺血性脑损伤和修复中的作用。 目的：观察脑缺血再灌注后成年模型大鼠大脑髓鞘蛋白相关基因,在脑缺血后不同时间及部位表达变化和差异。 方法：以线栓法制作成年SD大鼠局灶性脑缺血再灌注模型,采用5′末端标记地高辛的寡核苷酸探针荧光原位核酸分子杂交检测模型大鼠再灌注后早期大脑梗死中心区、梗死周边区和梗死对侧区皮质髓鞘蛋白脂质蛋白mRNA、髓鞘碱性蛋白mRNA和髓鞘转录因子1 mRNA表达变化。 结果与结论：在梗死中心区,脑缺血再灌注后早期3种髓鞘相关蛋白基因表达均明显减少;在梗死周边区,再灌注后1 d时3种髓鞘相关蛋白基因表达与对照组比较无明显变化,之后逐渐增加,至14 d时均高于对照组(P  < 0.05,0.01),以髓鞘转录因子1 mRNA阳性细胞数升高最早(7 d)最为显著(P < 0.01)。因此,成年SD大鼠脑缺血再灌注后急性期梗死周边区皮质髓鞘相关蛋白的基因表达增加,提示少突胶质前体细胞对脑缺血性损伤敏感,其可能参与了脑缺血后损伤的修复过程。     

Cerebral hypoxia-ischemia and middle cerebral artery occlusion induce expression of the cannabinoid CB2 receptor in the brain

Until recently the cannabinoid CB2 receptor was believed to be absent from the central nervous system. In this study we have identified CB2 expressing cells that appear in the rat brain following stroke and hypoxic-ischemia. At 3 days following surgery CB2-positive macrophages, deriving from resident microglia and/or invading monocytes appear on the lesioned side of the brain. By day 7, a mixed population of CB2-positive cells is present. Microglia-derived macrophages are the key cells in the first stages of brain inflammation, and a pivotal step in the neurodegeneration that follows the acute stage of injury. Thus, CB2 may be important in the brain during injury, and in inflammatory neurodegenerative disorders. The presence of CB2-positive cells in the brain following stroke may provide a novel strategy for cannabinoid-mediated intervention into stroke induced neurodegeneration without the psychoactive effects of CB1 receptor stimulation.     

脑缺血后小胶质细胞和星形胶质细胞“交叉对话”的研究进展

<正>生理状态下,小胶质细胞保持静息状态,依靠较细长的分支感应大脑实质微环境,是中枢神经系统（central nervous system,CNS）应对损伤的前哨[1]。星形胶质细胞数目多于小胶质细胞,约占所有胶质细胞总数的一半,被认为是CNS中功能最多的胶质细胞[2]。缺血性脑卒中主要表现为神经炎症和血脑屏障（blood-brain barrier,BBB）功能障碍。     

GABA(B) receptor expression and cellular localization in gerbil hippocampus after transient global ischemia

Using in situ hybridization, the expression of the GABA receptor subtype B subunit 1 (GABA(B) R1) and subunit 2 (GABA(B) R2) following transient global ischemia in the gerbil hippocampus was investigated. In sham-operated animals, mRNAs of both subunits were mainly detected in hippocampal pyramidal cells and interneurons with lower expression levels of the GABA(B) R2 in the CA1 field. Four days after transient cerebral ischemia, neuronal message decreased in conjunction with neuronal death and both receptor subunits disappeared from the pyramidal cell layer. However, GABA(B) R1 and GABA(B) R2 were still expressed in a few cells. In situ hybridization of the GABA synthesizing enzyme glutamic acid decarboxylase 67 (GAD67) remained unchanged after the ischemic insult. Double-labeling experiments revealed that in the postischemic hippocampus GABA(B) R1 and GABA(B) R2 were not present in GFAP-reactive astrocytes, but that the surviving parvalbumin-containing interneurons possessed GABA(B) R1 and GABA(B) R2 mRNA.     

四逆汤对大鼠局灶性脑缺血后bax、bcl-2表达的影响

目的：研究四逆汤对大鼠局部脑缺血后bax、bcl-2表达的影响。 方法： 采用大鼠大脑中动脉局部阻塞（MCAO）模型，观察四逆汤对脑缺血大鼠的神经功能、丙二醛（MDA）和神经酰胺含量、超氧化物歧化酶（SOD）活性以及bax、bcl-2表达的影响。 结果： 四逆汤组脑含水量、MDA含量、神经酰胺含量、bax基因在转录和翻译水平的表达明显低于缺血模型组（P<0.05和P<0.01），神经功能评分、SOD活性、Bcl-2蛋白的表达高于缺血模型组（P<0.05和P<0.01）。 结论： 四逆汤对局部脑缺血大鼠具有显著的保护作用，其作用机制可能与四逆汤能对抗脑缺血引起的氧化损伤，减少神经酰胺的生成量，抑制bax mRNA的转录及其蛋白的表达、增加Bcl-2蛋白的表达有关。     

动员造血干细胞对局灶性缺血再灌注大鼠脑组织C-FOS mRNA表达的影响

目的探讨应用粒细胞集落刺激因子(G-CSF)动员自体造血干细胞(HSC)对大脑中动脉栓塞/再灌注大鼠(MCAO/R)脑组织C-FOSmRNA表达的影响。方法制作MCAO/R模型;免疫组化双标记法鉴定HSC向神经元样细胞分化;RT-PCR法检测C-FOSmRNA表达水平。结果模型 G-CSF组再灌注后24 h出现CD34/Brdu双标记,48 h时双标记最为显著;再灌注后48 h出现CD34/NSE双标记。模型组各时间点C-FOSmRNA表达显著高于假手术组;G-CSF致再灌注48 h后C-FOSmRNA表达显著下调。结论应用G-GSF动员大鼠自体HSC可促进脑缺血再灌注损伤修复,调节C-FOSmRNA表达水平可能为其作用机制之一,而部分HSC来源的细胞分化为神经元样细胞可能参与缺血损伤修复过程。