大鼠脑出血后内源性神经干细胞激活和增殖的实验研究

目的 观察大鼠脑出血模型内源性神经干细胞(NSCs)的激活、增殖情况及其对神经行为学表现的影响.方法 将72只SD大鼠按单双号分为脑出血组和假手术组.每组36只.脑出血组利用立体定向技术,将一定量的Ⅳ型胶原酶用微量进样器分别精确注入大鼠内囊诱导脑出血模型.假手术组注射等量体积的PBS.分别于术后1、7、14、21、28和35 d观察大鼠的神经功能表现.所有大鼠处死前1 d腹腔内注射5.溴脱氧尿嘧啶(BrdU),免疫组织化学方法动态检测大鼠脑内巢蛋白(nestin)和BrdU的表达.结果 假手术组大鼠脑内未见nestin和BrdU的表达.脑出血组血肿周围基底节和脑室下区可见nestin和BrdU的表达.脑出血后7 d后开始明显增加.14 d达高峰,21 d开始下降.28d恢复正常.脑出血后l～35d大鼠神经功能无明显恢复,与内源性NSCs的增殖程度无明显相关.结论 脑出血可导致内源性NSCs的激活和诱导其增殖:然而这种状态下NSCs的增殖能力和内源性NSCs对脑出血后神经功能缺损的修复均有限.     

电刺激治疗对脑梗死大鼠运动功能和脑组织微管相关蛋白-2及存活素表达的影响

目的探讨电刺激对脑梗死大鼠运动功能和脑组织微管相关蛋白-2(MAP-2)及存活素表达的影响。方法采用线栓法制作大鼠局灶性脑梗死模型。制模后24h起,分别给予大鼠瘫痪侧(单侧)或双侧肢体电刺激治疗3d、7d、14d和21d。电刺激前、后各时间点用平衡木试验(BWT)检测大鼠的肢体运动功能,用免疫组化染色检测梗死灶周围大脑皮质MAP-2和存活素的表达水平,并与脑梗死对照组和假手术组大鼠比较。结果治疗第7d起电刺激组大鼠瘫痪肢体的BWT评分明显高于对照组(均P<0.05),治疗14d起双侧电刺激组BWT评分明显高于单侧电刺激组(均P<0.05)。治疗第7d起,电刺激组梗死灶周围脑组织MAP-2表达水平明显高于对照组(均P<0.05);治疗14d起,双侧电刺激组MAP-2的表达水平明显高于单侧电刺激组(均P<0.05);治疗21d时与假手术组MAP-2表达水平比较差异无统计学意义。电刺激组治疗后各时间点梗死灶周围脑组织存活素表达水平明显高于假手术组(均P<0.05),治疗7d、14d存活素表达水平明显高于对照组(均P<0.05),达到高峰;而双侧电刺激组明显高于单侧电刺激组(均P<0.05);治疗21d时,电刺激组和...     

不同电刺激对卒中后大鼠神经前体细胞增殖的影响

目的 探讨不同部位电刺激治疗对脑卒中后大鼠神经前体细胞增殖的作用.方法 选择2～3月龄,体质量80～120 g雄性SD大鼠95只,随机分为梗死灶周围电刺激组(A组)、肢体电刺激组(B组)、对照组(C组)和假手术组(D组).建立大脑中动脉闭塞模型,在术后24 h开始对两电刺激组大鼠头皮和肢体电刺激治疗.在梗死后7d、14d、21 d、28 d以横木行走试验(BWT)进行神经功能评分,同时进行室管膜和室管膜下5-溴脱氧尿嘧啶核苷(Brdu)的免疫组织化学检测.结果 A组及B组缺血后室管膜Brdu的表达与C组比较在7、14d差异均有统计学意义(P＜0.05),MCAO后7d二者相比Brdu 在室管膜和室管膜下区的表达差异有统计学意义(P＜0.05);MCAO后21dA组Brdu的表达和C组差异有统计学意义(P＜0.05),但此时B组和C组差异无统计学意义(P＞0.05);在MCAO后第1天及第28天三者之间的Brdu均有表达但差异无统计学意义(P＞0.05).结论 电刺激促进MCAO后神经干细胞的增殖,但梗死灶周围头皮电刺激治疗较肢体电刺激治疗引起的神经干细胞增殖明显.     

重复经颅磁刺激对脑梗死大鼠梗死侧皮质内源性神经干细胞激活、增殖的影响

目的研究重复经颅磁刺激(rTMS)对脑梗死大鼠神经功能恢复及梗死侧皮质内源性神经干细胞激活、增殖的影响。方法将72只雄性SD大鼠随机分为模型组、假刺激组、rTMS组,每组24只,各组根据脑梗死后不同时间点再分为1、7、14、21 d四个亚组,每个亚组6只。采用线栓法制作左侧大脑中动脉闭塞脑梗死模型。rTMS组于动物清醒后当天即给予每天2次、每次30个脉冲的rTMS治疗(频率为0.5 Hz,场强为1.33 T);假刺激组模拟rTMS固定大鼠头部放置线圈但不给予脉冲磁刺激;模型组不给任何治疗。各组在规定的时间点应用改良的神经功能缺损评分(mNSS)进行神经功能评定,治疗结束前24 h腹腔注射5-溴脱氧尿嘧啶核苷(BrdU),应用免疫组织化学技术检测梗死侧皮质巢蛋白(nestin)及BrdU表达阳性细胞的数量。结果 rTMS组脑梗死后7、14、21 d mNSS评分明显低于假刺激组及模型组同时间点大鼠(P<0.05),假刺激组及模型组大鼠脑梗死后不同时间点mNSS评分差异不明显(P>0.05)。脑梗死后1d模型组、假刺激组和rTMS组梗死灶周围皮质均可见nestin及BrdU阳性细胞,7 d达高峰。和假刺激组及模型组同时间点相比,rTMS组7、14、21 d nestin及BrdU阳性细胞数量明显增多,两者比较差异明显(P<0.05)。结论 rTMS能促进脑梗死大鼠神经功能恢复,机制可能与rTMS治疗能促进脑梗死周围内源性神经干细胞的激活及增殖有关。     

高压氧治疗对家兔实验性大脑中动脉闭塞后梗死灶周围巢蛋白表达的影响

目的 探讨高压氧(HBO)治疗对兔大脑中动脉闭塞(MCAO)模型梗死灶周围巢蛋白(nestin)表达的影响.方法 制备兔右侧MCAO模型.将动物分为3组,即MCAO+HBO治疗组(30只):MCAO后立即行HBO治疗,每天1次,连续20 d;MCAO对照组(30只):MCAO后不行HBO治疗;假手术组(10只):仅开颅不闭塞血管.分别于MCAO后10d、20 d观察其行为学、梗死体积变化.并用免疫组化法检测距梗死灶中心3 mm内皮层脑组织内nestin的表达.结果 MCAO后.MCAO+HBO治疗组行为学评分高于MCAO对照组,差异有统计学意义(P<0.05);MCAO+HBO治疗组脑梗死体积小于MCAO对照组,差异有统计学意义(P<0.05);MACO后10 d、20 dMCAO+HBO治疗组nestin免疫阳性细胞数05.88±1.2、20.03±1.6)高于MCAO对照组(6.63±1.6、6.82±0.8),差异有统计学意义(P<0.05).结论 早期、连续20 d HBO治疗对兔MCAO后的神经行为学、梗死体积有明显的治疗效果,并促进兔MCAO后梗死灶周围脑组织内nestin的表达.     

神经生长因子联合康复训练对脑梗死大鼠神经行为学及脑源性神经营养因子、Bax表达的影响

目的 研究神经生长因子(NGF)联合康复训练对脑梗死大鼠神经行为学及脑源性神经营养因子(BDNF)和促凋亡蛋白Bax表达的影响.方法 将72只SD大鼠随机分为对照组、NGF组、康复训练组及NGF联合康复训练治疗组(联合治疗组),每组又分为脑梗死后7d、14 d、21 d 3个亚组.采用线栓法制作脑梗死大鼠模型,NGF组制模后即予腹腔注射鼠NGF 20 μg/(kg·d);康复训练组制模后72 h给予平衡木、转棒、网屏训练;联合治疗组同时给予NGF和康复训练.各组分别于相应时间点进行神经行为学评分,采用免疫组化染色检测脑组织BDNF、Bax的表达,逆转录-PCR法检测BDNF mRNA、BaxmRNA的表达.结果 与对照组相比,NGF组、康复训练组及联合治疗组各时间点亚组的神经行为学评分均明显降低,脑组织BDNF、BDNFmRNA表达明显升高,Bax及Bax mRNA表达明显降低(均P＜0.05).与联合治疗组比较,NGF组、康复训练组各时间点亚组的神经行为学评分均明显升高,脑组织BDNF、BDNF mRNA水平明显降低,Bax、Bax mRNA表达水平明显增高(均P＜0.05).结论 NGF联合康复训练能上调BDNF、下调Bax的表达,而显著改善脑梗死大鼠的神经功能恢复.     

血管性认知障碍小鼠脑内少突胶质细胞再生分化障碍特点研究

目的 观察血管性认知障碍小鼠模型中,缺血性炎性损伤对室管膜下区及海马齿状回少突胶质细胞 再生分化的影响,为血管性认知障碍的缺血性炎症机制提出新的损伤途径。 方法 成年雄性CD1小鼠随机分为模型组和假手术组,每组24只,模型组采用双侧颈动脉反复缺 血再灌注法制备血管性认知障碍小鼠模型。造模后4～6 d连续腹腔注射5 -溴脱氧尿嘧啶核苷 （bromodeoxyuridine,BrdU）（150 mg/kg）标记新生细胞,分别于术后14 d和28 d每组随机取一半小鼠脑 组织进行脑切片免疫组化、免疫荧光双标共聚焦检测,标记脑组织室管膜下区和海马区的少突胶质 细胞、星形胶质细胞及神经元,观察新生少突胶质细胞增殖及分化情况,并观察星形胶质细胞的增 生活化情况。 结果 造模后14 d和28 d室管膜下区新生细胞（BrdU阳性细胞）在模型组较假手术组明显增加（P均 ＜0.001),造模28 d模型组新生神经元（BrdU/NeuN阳性细胞）较假手术组显著增加（P＜0.001)。与假 手术组相比较,术后28 d模型组海马齿状回少突胶质细胞祖细胞显著增多（P＜0.001）;少突胶质细 胞前体细胞显著减少（P =0.006）。造模后28 d模型组海马齿状回新生星形胶质细胞（BrdU/GFAP阳性 细胞）较假手术组显著增加（P =0.015）。 结论 血管性认知障碍小鼠内源性新生细胞增殖区室管膜下区与海马齿状回区均存在新生细胞反 应性增生的情况。新生细胞区分化的主要细胞为星形胶质细胞,而少突胶质细胞分化障碍,可能是血 管性认知障碍患者影像学常见皮层下白质病变的重要原因。     

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.     

表皮生长因子促进脑梗死后室管膜下区神经干细胞迁徙机制的初步研究

目的观察表皮生长因子（EGF）对大鼠脑梗死后室管膜下区（SVZ）神经干细胞（NSCs）的调节作用。方法采用肾血管性高血压大鼠复制成一侧大脑中动脉皮层支闭塞（MCAO）模型。MCAO）术后24h，64只EGF组大鼠侧脑室注入10μl EGF（0．1μg／μl），连续2d，共2μg；64只vehicle组大鼠只注入不含EGF的等量溶液。MCAO术后1、2、3和4周，免疫组化检测SVZ内巢蛋白（nestin），Western blotting检测双侧半球nestin、神经细胞粘附分子（NcAM）和瑞林蛋白（reelin）表达。结果与同期vehicle组相比，EGF组大鼠梗死灶同侧SVZ内nestin染色更强，可见从SVZ沿胼胝体向梗死灶迁徙的nestin阳性细胞带；Western blotting显示EGF促使脑梗死灶同侧nestin、NCAM和reelin更早期和更高的表达（P〈0．05）。结论EGF可能通过促使卒中后nestin、NCAM和reelin等神经可塑性物质的早期高峰表达而调节SVZ内NSCs增殖和向梗死灶迁徙。     

生物波调控因子对实验性脑梗死大鼠脑组织IL-6表达的影响

目的:探讨生物波调控因子(BRF)对实验性脑梗死大鼠脑组织IL-6表达的影响。方法:成年健康雄性SD大鼠90只随机分为BRF组、生理盐水组和假手术组。制备大脑中动脉梗死(MCAO)模型,术后1h以1ml/100g的剂量分别腹腔注射1.25%BRF溶液和生理盐水,此后1次/d。进行行为学评分、测定脑组织含水量、HE染色观察组织病理学改变、免疫组织化学方法测定脑组织IL-6的动态变化。结果:生理盐水组及BRF治疗组脑梗死组织周围组织含水量于24h开始明显升高,48h达高峰,持续至72h,7d时明显下降,在各个时间点与假手术组比较均有统计学意义。除假手术组外,其余各组梗死区炎细胞浸润和IL-6阳性细胞表达于梗死后6h开始增多,48h达高峰,并持续至7d;假手术组未见明显炎细胞浸润,可见少量IL-6阳性细胞。BRF治疗组大鼠行为学评分降低,脑组织水肿程度减轻,术后48h最显著,病理损伤减轻,脑组织IL-6阳性细胞减少,术后48h、72h最显著。结论:生物波调控因子可以通过减轻梗死后脑水肿,降低脑内IL-6的表达,从而对大鼠缺血性脑组织损伤产生保护作用。     

Transplantation of Flk-1+ human bone marrow-derived mesenchymal stem cells promotes angiogenesis and neurogenesis after cerebral ischemia in rats

Transplantation of bone marrow‐derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. Although BMSCs‐induced angiogenesis is considered important for neurological functional recovery, the neurorestorative mechanisms are not fully understood. We examined whether BMSCs‐induced angiogenesis enhances cerebral tissue perfusion and creates a suitable microenvironment within the ischemic brain, which in turn accelerates endogenous neurogenesis and leads to improved functional recovery. Adult female rats subjected to 2 h middle cerebral artery occlusion (MCAO) were transplanted with a subpopulation of human BMSCs from male donors (Flk‐1+ hBMSCs) or saline into the ipsilateral brain parenchymal at 3 days after MCAO. Flk‐1+ hBMSCs‐treated rats exhibited significant behavioral recovery, beginning at 2 weeks after cerebral ischemia compared with controls. Moreover, rats treated with Flk‐1+ hBMSCs showed increased glucose metabolic activity and reduced infarct volume. Flk‐1+ hBMSCs treatment significantly increased the expression of vascular endothelial growth factor and brain‐derived neurotrophic factor, promoted angiogenesis, and facilitated cerebral blood flow in the ischemic boundary zone. Further, Flk‐1+ hBMSCs treatment enhanced proliferation of neural stem/progenitor cells (NSPCs) in the subventricular zone and subgranular zone of the hippocampus. Finally, more NSPCs migrated toward the ischemic lesion and differentiated to mature neurons or glial cells with less apoptosis in Flk‐1+ hBMSCs‐treated rats. These data indicate that angiogenesis induced by Flk‐1+ hBMSCs promotes endogenous neurogenesis, which may cause functional recovery after cerebral ischemia.     

丰富环境对脑梗死大鼠学习记忆和海马区微血管密度的影响

目的 研究丰富环境对局灶性脑梗死大鼠学习记忆及海马区微血管密度的影响.方法 采用开颅电凝法制作SD大鼠右侧大脑中动脉缺血(MCAO)模型,术后24h随机分为丰富环境组(EE组)和标准环境组(SE组),另设假手术组(Sham组),不电凝大脑中动脉,其余步骤与手术组相同.分别于术后7d、28d进行Mornis水迷宫测试大鼠学习记忆能力;以免疫组织化学法测定海马区微血管密度.结果 在学习记忆能力上,EE组成绩明显优于SE组(P<0.01),与Sham组相比无显著性差异(P>0.05);缺血侧海马区微血管密度显示EE组在术后14d、28d明显高于SE组大鼠(P<0.05),与Sham组相比无显著性差异(P>0.05).结论 丰富环境可促进脑梗死大鼠学习记忆能力的恢复与海马区微血管新生,改善大鼠的预后.

Abstract：

Objective To evaluate the effect of enriched environment on learning and memory and microvessel density in hippocampus of rats after unilateral local cerebral infarction. Methods The right middle cerebral artery occlusion (MCAO) was performed with electric coagulation in SD rats, then the rats were randomly divided into enriched environment stimulation group (EE group) and standard environment stimulation group (SE group). The sham-operation rats were as control group. On 7d and 28d, Morris water maze was used to evaluate the learning and memory ability;microvessel density in hippocampus of rats was measured in the boundary zone to brain infarction on 1d,3d,7d,14d and 28d. Result The learning and memory ability in EE group was significantly better than that in SE group ( P < 0.01 ) and there was no significant difference between EE group and Sham group (P > 0.05 ) ;Compared with SE group, the microvessel density (MVD) of EE group in hippocampus of rats significantly increased on 14d and 28d after MCAO( P <0.05). There was no significant difference in MVD between EE group and sham group (P > 0.05 ). Conclusion The enriched environment can enhance the ability of learning and memory and promote the blood vessel proliferation of rats with unilateral local cerebral infarction.The study suggests enriched environment is good for recovery from brain damage in rats with MCAO.     

Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2′-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2′- deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.     

Therapeutic effects of lipo-prostaglandin E1 on angiogenesis and neurogenesis after ischemic stroke in rats

Previous studies have demonstrated that prostaglandin E1 (PGE1) has a neuroprotective effect on cerebral ischemia. However, it remains unknown whether PGE1 promotes angiogenesis and neurogenesis after ischemic stroke. In this study, adult male Sprague-Dawley rats were subjected to permanently distal middle cerebral artery occlusion (MCAO). Rats were treated with lipo-prostaglandin E1(lipo-PGE1, 10 μg/kg/d) or the same volume of 0.9% saline starting 24 hours after MCAO daily for 6 consecutive days. All rats were injected 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg) intraperitoneally every 12 hours for 3 consecutive days before being sacrificed. At 7 and 14 days after MCAO or sham-operation, rats were sacrificed. Post-stroke neurological outcome, infarction volume, angiogenesis and neurogenesis were evaluated. Treatment with lipo-PGE1 significantly increased the vascular density in the peri-infarct areas at 7 and 14 days after MCAO. The lipo-PGE1 treatment significantly enhanced the proliferation and migration of endogenous neural stem cells in the ipsilateral subventricular zone. The neural stem cells associated with blood vessels closely within a neurovascular niche in lipo-PGE1-treated rats after stroke. The lipo-PGE1 treatment also significantly improved the neurological recovery after MCAO. These results indicate that treatment with lipo-PGE1 promotes post-stroke angiogenesis, neurogenesis and their interaction, which would contribute to neurological recovery after cerebral infarction. Our study provides novel experimental evidences for the neuroprotective roles of PGE1 in ischemic stroke.     

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。     

骨髓基质干细胞移植对缺血性卒中大鼠PSD-95表达的影响

目的 应用骨髓基质干细胞（BMSCs）治疗缺血性卒中大鼠,观察BMSCs的治疗效果,检测突触后密度蛋白-95（PSD-95）的表达水平,进而研究BMSCs治疗缺血性卒中的机制.方法 将40只成年雌性SD大鼠制备成大脑中动脉缺血2h再灌注24h动物模型,随机分为梗死对照组和BMSCs组,每组20只.每组再按梗死后3,7d分为2个亚组,每组10只.梗死对照组于缺血再灌注24 h后经尾静脉注射PBS液1ml,BMSCs组同时经尾静脉注射BMSCs 3×106.所有大鼠于梗死后1,3,7d分别进行神经功能评分,应用免疫组化法测定PSD-95表达水平,用TUNEL测定凋亡细胞水平.结果 （1）神经功能评分：梗死后3,7 d BMSCs组神经功能评分明显低于梗死对照组,差异有统计学意义（t分别为2.138,3.417;P＜0.05）.（2） PSD-95表达：BMSCs组在梗死后3d时PSD-95表达较梗死对照组的表达有增多,但差异无统计学意义;BMSCs组在梗死后7d时PSD-95表达明显多于梗死对照组,且差异有统计学意义（t=6.013,P＜0.05）.（3）TUNEL细胞凋亡染色：梗死后3d时梗死对照组大鼠缺血侧可见许多凋亡细胞,显多于BMSCs组,且差异有统计学意义（t=4.978,P＜ 0.05）.结论 BMSCs移植能促进缺血性卒中大鼠的神经功能的恢复.BMSCs移植后能明显增加缺血性卒中大鼠PSD-95的表达,减少细胞的凋亡,对缺血性卒中有保护作用.     

脑室内注射碱性成纤维细胞生长因子治疗大鼠创伤生脑外伤的实验研究

目的 探讨脑室内注射碱性成纤维细胞生长因子(bFGF)对创伤性脑外伤大鼠是否具有治疗作用. 方法 24只成年SD大鼠按随机数字表法分为治疗组和对照组,采用改良的Feeney氏自由落体撞击方法建立大鼠创伤性脑外伤模型,致伤后24 h分别给予脑室内注射bFGF和等量的生理盐水;采用行为测试试验(前肢放置试验、平衡试验)评分观察肢体功能恢复情况;采用免疫组化法,以5溴脱氧嘧啶尿苷(Brdu)标记神经干细胞,观察并比较两组大鼠致伤后第3、7、14天侧脑室室管膜下区(SVZ)、海马齿状回及损伤区域Brdu阳性细胞的表达. 结果 治疗组前肢放置试验评分在第3～12天、平衡试验在第3～11天的评分低于对照组,比较差异有统汁学意义(P<0.05).治疗组双侧SVZ、海马齿状回和损伤区域出现的Brdu阳性细胞数较对照组明显增多,差异有统计学意义(P<0.05).两组损伤侧Brdu阳性细胞数均高于损伤对侧,比较差异有统计学意义(P<0.05).行为学评分与Brdu阳性细胞数之间呈负相关关系. 结论 脑室内注射bFGF有助于创伤性脑外伤大鼠模型内源性神经干细胞的增殖,并能促进其肢体功能的恢复.