卡马西平对匹罗卡品诱导成年癫间疒大鼠海马齿状回神经前体细胞增殖的影响

目的研究卡马西平对成年癫大鼠海马齿状回内源性神经前体细胞增殖的影响。方法采用氯化锂和匹罗卡品联合诱导大鼠癫模型,将癫大鼠随机分为癫对照组和癫卡马西平组,正常大鼠随机分为正常对照组和正常卡马西平组。癫对照组和正常对照组给以蒸馏水灌胃,同时癫卡马西平组和正常卡马西平组给予卡马西平灌胃。于灌胃后第6d腹腔注射5-溴脱氧尿苷嘧啶(BrdU)标记海马齿状回的内源性神经前体细胞的增殖情况;用免疫组化方法观察各组大鼠在注射BrdU后第1d、第7d齿状回BrdU阳性细胞数量的表达。结果①注射BrdU后第1d,癫对照组大鼠海马齿状回BrdU阳性细胞数较正常对照组明显增加(P<0.01),癫卡马西平组大鼠海马齿状回BrdU阳性细胞数较癫对照组减少(P<0.05);②注射BrdU后第7d,癫对照组大鼠海马齿状回BrdU阳性细胞数较正常对照组明显增加(P<0.01),癫卡马西平组大鼠海马齿状回BrdU阳性细胞数较癫对照组明显减少(P<0.05)。结论卡马西平抑制癫大鼠海马齿状回内源性神经前体细胞增殖。     

Orexin-1受体拮抗剂对慢性点燃癫大鼠学习记忆的影响及海马神经细胞的增殖变化

目的:研究orexin-1受体(OX1R)拮抗剂(SB334867,SB)对戊四氮(PTZ)慢性点燃癫大鼠空间学习记忆能力及海马齿状回神经细胞增殖的影响。方法:Wistar大鼠随机分为①对照组[腹腔和侧脑室均注射生理盐水(NS)];②PTZ组(腹腔注射PTZ+侧脑室注射NS);③PTZ+orexin-A(OXA)组(腹腔注射PTZ+侧脑室注射OXA);④PTZ+SB组(腹腔注射PTZ+侧脑室注射SB);⑤PTZ+SB+OXA组(腹腔注射PTZ+侧脑室注射SB和OXA)。观察各组大鼠的空间学习记忆能力及海马齿状回区BrdU+和BrdU+/NeuN+细胞的表达。结果:与PTZ+OXA组比较,PTZ+SB+OXA组大鼠逃避潜伏期延长、穿越平台象限的次数减少(P<0.05)。免疫荧光显示,PTZ+OXA组大鼠齿状回区BrdU+和BrdU+/NeuN+细胞表达增多(P<0.01),而PTZ+SB+OXA组大鼠齿状回区BrdU+/NeuN+细胞表达比PTZ+OXA组减少(P<0.01)。结论:OXA通过OX1R能改善癫大鼠的空间学习记忆能力,可能与OX1R介导的海马齿状回神经细胞增殖与分化作用有关。     

老年大鼠脑出血后海马齿状回神经干细胞的增殖与分化

目的 观察老年大鼠脑出血后海马齿状回神经干细胞(NSCs)的增殖与分化,探讨脑出血后NSCs的变化规律.方法 制作老年大鼠脑出血模型,5-溴脱氧尿核苷(BrdU)腹腔注射标记增殖细胞,用免疫组化法检测大鼠海马齿状回BrdU、神经元核抗原(NeuN)、胶质纤维酸性蛋白(GFAP)阳性细胞数的变化.结果 正常组和假手术组老年大鼠海马齿状回均有少量BrdU阳性细胞,脑出血后大鼠各时间段的BrdU阳性细胞数目均较正常组和假手术组明显增加,7d组达到峰值后逐渐下降,28d组仍高于正常组和假手术组.正常老年大鼠海马齿状回可见少量BrdU/NeuN和BrdU/GFAP双标阳性细胞,脑出血后双标阳性细胞数较正常组明显增加.结论 脑出血后老年大鼠海马齿状回NSCs增殖明显,且可以向神经元和神经胶质细胞分化.     

卡马西平对成年癫大鼠海马齿状回BrdU/NeuN表达水平及其对空间记忆的影响

目的研究卡马西平对成年癫大鼠海马齿状回新生神经元的影响及其与空间记忆之间的关系。方法采用氯化锂和匹罗卡品联合诱导大鼠癫模型,利用5-溴脱氧尿苷嘧啶与神经元核性蛋白双标记观察海马齿状回内源性神经前体细胞分化为成熟神经元的情况;利用行为学分析评价大鼠的空间记忆。结果 (1)卡马西平可增加癫大鼠海马齿状回新生成熟神经元的数量(P<0.05);(2)卡马西平对癫大鼠的空间记忆有明显改善作用(P<0.01)。结论卡马西平增加癫大鼠海马齿状回新生成熟神经元形成,是其改善癫大鼠空间记忆的可能机制之一。     

慢性应激抑制卒中后大鼠海马内源性神经干细胞增殖和分化研究

目的 观察慢性应激对卒中后海马内源性神经干细胞增殖和分化的影响。方法 将雄性SD大鼠分为正常、卒中、慢性应激组。建立左侧大脑中动脉闭塞卒中动物模型并予以慢性不可预见温和应激刺激结合孤养。经溴脱氧尿苷嘧啶（BrdU）标记，免疫组化、荧光双标染色及共聚焦成像动态检测并比较各研究组大鼠左侧海马齿状回BrdU及其与神经元核性蛋白（NeuN）共表达。结果 与卒中组相比，慢性应激组大鼠病灶侧海马齿状回BrdU+细胞数在脑梗死后第7天未见减少，第21天明显减少（28.5±1.9 vs 72.2±1.4），差异有统计学意义（P<0.001）。与卒中组相比，慢性应激组大鼠病灶侧海马齿状回BrdU+/NeuN+细胞比例在脑梗死后30 d[（69.0±3.4）%）]和45 d[（78.3±2.4）%]均明显减少，差异有统计学意义（P<0.001； P<0.01）。结论 慢性应激能明显抑制卒中后海马内源性神经干细胞的增殖和分化，可能是卒中后抑郁发病的因素之一。     

丰富环境对成年颞叶癫大鼠认知功能及神经发生的影响

目的对成年颞叶癫大鼠进行丰富环境干预,探讨丰富环境是否能促进认知功能以及是否对齿状回的神经发生产生影响。方法将成年Wistar大鼠随机分为4组:假手术组、丰富环境+假手术组、癫组、丰富环境+癫组。丰富环境干预30 d后,应用Morris水迷宫实验进行学习记忆功能评价,并应用免疫荧光技术观察海马齿状回新生神经细胞的情况。结果一般线性重复变量分析示逃避潜伏期[F(3,36)=9.810,P0.05)]、上台前路程[F(3,36)=11.092,P0.05)],各组间差异有显著性;而游泳速度差异无显著性[F(3,36)=0.776,P0.05)]。丰富环境+假手术组海马齿状回DCX阳性细胞(新生神经细胞标志物)[(65.00±6.10)个]显著多于假手术组[(32.43±2.76)个](P0.05),癫组DCX阳性细胞[(21.30±2.97)个]较假手术组明显减少(P0.05);丰富环境+癫组DCX阳性细胞[(51.50±3.16)个]明显多于癫组(P0.05)。结论丰富环境有利于成年颞叶癫大鼠认知功能的恢复。     

学习记忆能力下降大鼠神经细胞增殖的研究

目的　观察学习记忆能力减退老年大鼠海马齿状回神经细胞的增殖。方法　Morris水迷宫筛选出学习记忆能力减退大鼠 (痴呆组 )与正常大鼠 (对照组 )。BrdU标记海马齿状回增殖细胞。TUNEL法标记DNA片段原位检测凋亡细胞。计数海马颗粒细胞层与海马门的BrdU阳性细胞与凋亡细胞数。结果　痴呆组与对照组大鼠相比 ,海马颗粒细胞层BrdU阳性细胞显著增加 (P <0 0 1) ,而凋亡细胞数无显著差异 (P >0 0 5 )。海马门BrdU阳性细胞数及凋亡细胞数均无显著差异 (P >0 0 5 )。结论　学习记忆能力减退的老年大鼠海马齿状回神经细胞增殖能力减低。     

丰富环境促进颞叶癫(痫)大鼠神经发生及其机制的研究

目的 探讨丰富环境对颞叶癫(痫)大鼠齿状回新生细胞分化和存活的影响及其相关分子机制.方法 成年Wistar 大鼠随机分为4组:假手术组、丰富环境+假手术组、癫(痫)组、丰富环境+癫(痫)组,各组均n=15.大鼠侧脑室注射海人酸制作颞叶癫(痫)模型.丰富环境干预30 d后,应用免疫荧光技术观察大鼠海马齿状回的新生细胞分化和存活情况,用Western blot方法检测各组海马脑源性神经营养因子(BDNF)、cAMP应答元件结合蛋白(pCREB)、蛋白激酶A(PKA)表达水平.结果 丰富环境+假手术组、丰富环境+癫(痫)组齿状回新生细胞标记物(BrdU)和新生成熟神经细胞标记物(BrdU/NeuN)阳性细胞数分别多于假手术组、癫(痫)组(P＜0.05),而新生星形胶质细胞BrdU/GFAP阳性细胞数无统计学意义,并且丰富环境+假手术组、丰富环境+癫(痫)组海马BDNF和pCREB蛋白表达水平分别高于假手术组、癫(痫)组(P＜o.05),而PKA蛋白表达水平无增高.结论 丰富环境可能通过增强pCREB/BDNF通路促进成年颞叶癫(痫)大鼠海马齿状回的神经发生.     

脑卒中后抑郁大鼠海马原位增殖的新生细胞存活和分化状态

目的 观察脑卒中后抑郁(post-stroke depression,PSD)大鼠海马原位增殖新生细胞的存活和分化.方法 采用左侧大脑中动脉阻塞(MCAO)联合慢性不可预见温和应激刺激(chronicmild stress,CMS)及孤养法建立PSD模型,将雄性SD大鼠分为假手术、脑卒中、CMS和PSD组.每组均为18只.采取免疫组织化学、荧光双标染色及共聚焦成像动态检测,比较各研究组大鼠左侧海马齿状回溴脱氧尿苷嘧啶(BrdU)及其与神经元特异性核蛋白(NeuN)或胶质纤维酸性蛋白(GFAP)共表达.结果 与脑卒中组(232.2±8.6、123.7±2.6、136.2±2.6)相比,PSD组大鼠左侧(伤侧)海马齿状回BrdU+细胞数在脑梗死后第21(156.2±2.5)、30(70.2±2.0)和45天(81.2±1.1)均明显减少(t=28.83、52.2、62.08,均P<0.01),但仍高于假手术组.与脑卒中组(79.3%±2.8%、87.7%±4.6%)相比,PSD组大鼠左侧(伤侧)海马齿状回BrdU+/NeuN+细胞比例在脑梗死后第30(69.0%±3.4%)和45天(78.3%±2.4%)均明显减少(t=5.871、4.403,均P<0.01).BrdU+/GFAP+细胞比例在脑梗死后30和45 d均明显增加(t=4.226、8.945,P<0.01).结论 PSD大鼠脑卒中后海马齿状回原位增殖的新生细胞存活降低,分化为神经元的比例下降,胶质细胞比例增加.     

卡马西平对成年癫癎大鼠海马齿状回BrdU/NeuN表达水平及其对空间记忆的影响

目的 研究卡马西平对成年癫癎大鼠海马齿状回新生神经元的影响及其与空间记忆之间的关系.方法 采用氯化锂和匹罗卡品联合诱导大鼠癫痫 间模型,利用5-溴脱氧尿苷嘧啶与神经元核性蛋白双标记观察海马齿状回内源性神经前体细胞分化为成熟神经元的情况;利用行为学分析评价大鼠的空间记忆.结果 (1)卡马西平可增加癫癎大鼠海马齿状回新生成熟神经元的数量(P＜0.05);(2)卡马西平对癫癎大鼠的空间记忆有明显改善作用(P＜0.01).结论 卡马西平增加癫癎大鼠海马齿状回新生成熟神经元形成,是其改善癫癎大鼠空间记忆的可能机制之一.     

匹罗卡品诱发成年大鼠普遍癫痫与难治性癫痫海马神经发生的变化

背景：神经发生包括细胞增殖、迁移、分化和存活等,是人和多数哺乳动物部分脑区产生新生神经元的过程,主要分布在侧脑室下区和海马齿状回。癫痫可导致海马齿状回的神经发生改变,BrdU是目前公认最理想检测未成熟细胞增殖的标记物之一。 目的：观察匹罗卡品诱发成年大鼠癫痫后神经发生的特点,以及普通癫痫与难治性癫痫神经发生的差异。 设计、时间及地点：随机分组,细胞分子生物学实验,于2006-08/2007-06在华中科技大学同济医学院中心实验室及附属协和医院中心实验室完成。 材料：选用健康Sprague-Dawley雄性大鼠100只,随机分为2组,对照组8只,实验组92只,分为普通癫痫组,自发发作组,难治性癫痫组和非耐药组。匹罗卡品为武汉晶美公司产品,兔抗鼠BrdU抗体为美国sigma公司产品,辣根过氧化物酶标记的羊抗兔IgG为武汉博士德公司产品。 方法：对照组大鼠腹腔注射生理盐水;实验组腹腔注射匹罗卡品15mg/kg,最多注射4次,出现癫痫持续状态的大鼠注射水合氯醛终止发作。致癫大鼠癫痫发作终止后6h腹腔注射BrdU,观察自发发作情况。以脑电图、自发发作频率持续时间,无自发发作为普通癫痫组,有自发发作为自发发作组。行卡马西平灌胃2周并记录发作频率,对卡马西平治疗无效,发作频率减少<50%的为难治性癫痫组,治疗有效即发作频率减少>50%为非耐药组。普通癫痫组分别于注射后第1,2,3,7,14,21和28d取鼠脑海马部做冠状连续切片。非耐药组和难治性癫痫组的大鼠,再次行腹腔注射BrdU,每次为50mg/kg,连续注射4次,每次间隔2h,48h后取脑海马部制作石蜡切片。 主要观察指标：脑海马部切片行免疫组化染色,镜下观察不同时间点BrdU阳性细胞的分布、形态和数量及注射匹罗卡品后大鼠癫痫发作状况。 结果：匹罗卡品第1次注射后所有大鼠无癫痫发作,第2次注射发作16只,第3次注射发作42只,第4次注射后发作11只,14只大鼠4次注射仍无癫痫发作,9只大鼠癫痫持续状态后死亡,77只进入结果分析。神经发生主要位于海马颗粒细胞层和齿状回。与对照组比较,普通癫痫组BrdU阳性细胞明显增多（P<0.01）,难治性癫痫组新生细胞较普通癫痫组明显减少（P<0.01）,神经发生减少。癫痫后第2天BrdU 阳性细胞数目开始增加,14-15d达到高峰,1个月后回到初始水平。 结论：与普通癫痫相比,难治性癫痫可导致神经发生减少。     

Granule cell dispersion develops without neurogenesis and does not fully depend on astroglial cell generation in a mouse model of temporal lobe epilepsy

Purpose: Granule cell dispersion (GCD) appears as a characteristic morphological feature of the mesial temporal lobe epilepsy (MTLE). It has been suggested that this phenomenon could be due to an increased neurogenesis in the dentate gyrus. However, this hypothesis is still debated and recent clinical and experimental studies have shown that neurogenesis is rather decreased in MTLE. To further determine the role of neural and astroglial cell generation in GCD we examined the consequences of aging and irradiation, which are known to reduce progenitor cells, in a mouse model of MTLE induced by intrahippocampal kainate (KA) injection. Methods: We injected KA in hippocampus of three different types of mice; (1) young adult, (2) aged, and (3) irradiated mice. Newly generated cells were labeled by Bromodeoxyuridine (BrdU) and were characterized by immunohistochemistry. The extent of GCD was compared among the three animal groups. Results: In young adult mice, BrdU‐labeled neurons as well as doublecortin‐ and NeuroD‐positive cells decreased progressively after KA injection whereas BrdU‐labeled astrocytes and microglias increased. In aged and irradiated mice, where basal neurogenesis was already strongly reduced, GCD developed after KA injection to the same extent as in young adult mice. However, augmentation of the BrdU‐labeled astrocytes after KA was less than 40% in irradiated mice in comparison to young and aged mice. Conclusions: Our data show that GCD occurs without neurogenesis. Furthermore GCD developed regardless of the degree of astroglial cell proliferation, suggesting that neural stem cell generation is not crucial for GCD.     

Peripheral nerve regeneration by bone marrow stromal cells

Adult bone marrow contains stem cells that have attracted interest through their possible use for cell therapy in neurological diseases. Bone marrow stromal cells (MSCs) were harvested from donor adult rats, cultured and pre-labeled with bromodeoxyuridine (BrdU) previously to be injected in the distal stump of transected sciatic nerve of the rats. Distal nerve stump of control rats received culture medium solution. MSCs-treated rats exhibit significant improvement on walking track test at days 18 and 33 compared to controls. Dual immunofluorescence labeling shows that BrdU reactive cells survive in the injected area of transected sciatic nerve at least 33 days after implantation, and almost 5% of BrdU cells express Schwann cell-like phenotype (S100 immunoreactivity). Because MSCs injected in a lesioned peripheral nerve can survive, migrate, differentiate in Schwann cells, and promote functional recovery, they may be an important source for cellular therapy in several neurological diseases.     

Effects of Abeta25-35 on neurogenesis in the adult mouse subventricular zone and dentate gyrus

It has been demonstrated that neuorgenesis driven by neural precursor cells persists well into the adult period. This study was to observe the effects of Amyloid-beta (25-35) peptide (Abeta(25-35)) on neurogenesis in the subventricular zone and dentate gyrus of adult mouse brain. Aggregated Abeta(25-35)(1 mg/ml, 3 microl) was injected into the lateral ventricle of adult mouse. Animals were transcardially perfused with 4% paraformaldehyde in PBS, respectively at 5, 10, 20, 30 days after the Abeta(25-35) injection. All the animals were injected with BrdU (50 mg/kg, i. p) to label the neural precursor cells 24 h before the each perfusion. NeuN immunofluorescence and BrdU immunohistology were performed. It was found that Abeta(25-35) could injure the mature neurons and decrease the number of NeuN positive neurons. It also showed that Abeta(25-35) inhibited neurogenesis and significantly decreased the number of BrdU positive cells in the dentate gyrus of hippocampus, but it had no obvious effects on neurogenesis in the subventricular zone. The present results indicated that Abeta(25-35) could impair neurogenesis in the hippocampus of adult mouse brain.     

The Alzheimer's disease drug memantine increases the number of radial glia‐like progenitor cells in adult hippocampus

New neurons are continuously generated in the hippocampus of the adult mammalian brain, and N‐methyl‐D ‐aspartate receptor (NMDA‐R) antagonists have been found to increase the number of newly generated neurons in the dentate gyrus (DG) of the adult hippocampus. In this study, we examined the effect of memantine, an NMDA‐R antagonist that is clinically used for the treatment of Alzheimer's disease, on primary progenitor cells exhibiting a radial glia‐like (RGL) morphology in the DG. We injected 3‐month‐old mice with memantine (50 mg/kg body weight, intraperitoneally [i.p.]); 3 days later, we injected the mice with 5‐bromo‐2‐deoxyuridine (BrdU; 75 mg/kg body weight, i.p.). We then counted the number of BrdU‐labeled RGL progenitor cells in the DG 1 or 7 days after the BrdU‐injection. The number of BrdU‐labeled RGL progenitor cells had increased significantly by 5.1‐fold on day 1 and by 13.7‐fold on day 7 after BrdU‐injection. Immunohistochemical staining revealed that the BrdU‐labeled RGL progenitor cells expressed two primary progenitor cell marker proteins, nestin and Sox2. These results clearly demonstrated that memantine promotes the proliferation of RGL progenitor cells. We also found that memantine increased the ratio of horizontally aligned RGL progenitor cells, which are probably produced by symmetric division. These findings suggest that memantine increases the proliferation of primary progenitor cells and expands the primary progenitor cell pool in the adult hippocampus by stimulating symmetric division. © 2008 Wiley‐Liss, Inc.     

Short-term and long-term survival of new neurons in the rat dentate gyrus

New neurons continue to be generated in the dentate gyrus throughout adulthood. Previous studies have shown that a significant proportion of new granule cells labeled with the thymidine analogue bromodeoxyuridine (BrdU) are lost from the adult dentate gyrus within 2 weeks. How long this loss continues and the extent to which it represents cell death, as opposed to dilution of label, is unclear. To address these questions, adult rats were injected with BrdU, and BrdU labeling in the dentate gyrus was compared at several survival time points. Double labeling with BrdU and the cell cycle marker Ki-67 showed that BrdU is detectable for up to 4 days in some cells that continue to divide, indicating that any decrease in the number of BrdU-labeled cells after 4 days is likely to reflect cell death rather than BrdU dilution. Death of new cells in the granule cell layer occurred at a steady rate between 6 and 28 days after labeling, resulting in loss of 50% of BrdU-labeled cells over this 22-day period. New granule cells that survived this first month lived for at least 5 additional months. In contrast, 26% of the granule cells labeled with BrdU at the peak of dentate gyrus development on postnatal day (P) 6 died between 1 and 6 months after labeling. These findings suggest that granule cells born during adulthood that become integrated into circuits and survive to maturity are very stable and may permanently replace granule cells born during development.     

Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice.

The authors transplanted adult bone marrow nonhematopoietic cells into the striatum after embolic middle cerebral artery occlusion (MCAO). Mice (n = 23; C57BL/6J) were divided into four groups: (1) mice (n = 5) were subjected to MCAO and transplanted with bone marrow nonhematopoietic cells (prelabeled by bromodeoxyuridine, BrdU) into the ischemic striatum, (2) MCAO alone (n = 8), (3) MCAO with injection of phosphate buffered saline (n = 5), and (4) bone marrow nonhematopoietic cells injected into the normal striatum (n = 5). Mice were killed at 28 days after stroke. BrdU reactive cells survived and migrated a distance of approximately 2.2 mm from the grafting areas toward the ischemic areas. BrdU reactive cells expressed the neuronal specific protein NeuN in 1% of BrdU stained cells and the astrocytic specific protein glial fibrillary acidic protein (GFAP) in 8% of the BrdU stained cells. Functional recovery from a rotarod test (P < 0.05) and modified neurologic severity score tests (including motor, sensory, and reflex; P < 0.05) were significantly improved in the mice receiving bone marrow nonhematopoietic cells compared with MCAO alone. The current findings suggest that the intrastriatal transplanted bone marrow nonhematopoietic cells survived in the ischemic brain and improved functional recovery of adult mice even though infarct volumes did not change significantly. Bone marrow nonhematopoietic cells may provide a new avenue to promote recovery of injured brain.     

Efficacy of doublecortin as a marker to analyse the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus

Doublecortin (DCX), a microtubule-associated phosphoprotein, has been recently utilized as a marker of newly born neurons in the adult dentate gyrus (DG). Nonetheless, it is unknown whether DCX exclusively labels newly formed neurons, as certain granule cells with the phenotype of differentiated neurons express DCX. We addressed the authenticity of DCX as a marker of new neurons in the adult DG by quantifying cells that are positive for 5'-bromodeoxyuridine (BrdU), DCX and both BrdU and DCX in hippocampal tissues of adult rats treated with daily injections of BrdU for 12 consecutive days. We provide new evidence that neurons visualized with DCX immunostaining in the adult rat DG are new neurons that are predominantly born during the 12 days before euthanasia. This is confirmed by the robust expression of BrdU in 90% of DCX-positive neurons in the DG of animals injected with BrdU for 12 days. Furthermore, DCX expression is specific to newly generated healthy neurons, as virtually all DCX-positive cells express early neuronal antigens but lack antigens specific to glia, undifferentiated cells or apoptotic cells. As DCX expression is also robust in the dendrites, DCX immunocytochemistry of thicker sections facilitates quantification of the dendritic growth in newly born neurons. Thus, both absolute number and dendritic growth of new neurons that are generated in the adult DG over a 12-day period can be quantified reliably with DCX immunostaining. This could be particularly useful for analysing changes in dentate neurogenesis in human hippocampal tissues as a function of ageing or neurodegenerative diseases.     

GDNF对局灶性脑缺血大鼠SVZ和SGZ细胞增殖及学习记忆的影响

目的　观察胶质细胞源性神经营养因子(GDNF)对局灶性脑缺血再灌注大鼠SVZ和SGZ细胞增殖的影响。方法　大脑中动脉线栓法制作大鼠局灶性脑缺血再灌注模型,立体定位下侧脑室注射GDNF,应用5 -溴脱氧尿核苷(Brd U )标记分裂细胞,观察模型组、GDNF组大鼠SVZ和SGZ神经干细胞的增殖,同时应用Y迷宫监测大鼠学习记忆能力。结果　局灶性脑缺血再灌注损伤大鼠GDNF组神经干细胞增殖明显增加,Brd U免疫阳性细胞数与相应对照组比较,差异有显著性意义(P<0 .0 5 )。GDNF组大鼠学习和记忆能力与相应对照组比较,差异有显著性(P<0 .0 5 )。结论　GDNF可增强局灶性脑缺血SVZ和SGZ细胞增殖能力,外源性GDNF可加速中枢神经损伤的修复。