摘要
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(chronic mild 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45d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。
Objective To investigate the proliferation and survival of endogenous new born cells in the hippocarnpus of post-stroke depression (PSD) rats. Methods Male SD rats were divided into 4 groups ( n = 18 ) : control, stroke, depression and PSD group. The animals were subjected to left middle cerebral artery occlusion (MCAO) reauhing in consistent focal cerebral infarcts, followed by an 18-day exposure to chronic mild stress (CMS) and single housing to induce PSD animal model. The dynamic expression of brodmodeoxyuridine (BrdU), neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) in the left dentate gyms of hippocampus were determined by immunohistochemistry or double-lable immunofluorescence staining. BrdU was a marker of new born cell, NeuN and GFAP marked that new born cell differentiated into neuron and astrocyte respectively. Results Compared with ischemia animals ( 232. 2±8.6,123.7±2. 6,136. 2±2. 6 ) , in the left dentate gyms, PSD samples had significantly less BrdU-positive cells ( 156. 2±2. 5, t = 28.83, P 〈0. 01 ) on the 21st day after ischemia, and on day 30 and 45 (70. 2±2.0, 81.2±1.1, t = 52. 27, 62. 08, both P 〈 0. 01 ). The ratio of BrdU-positive cells to NeuN had decreased on day 30 (79. 3%±2. 8% vs 69.0%±3.4% , t = 5. 871, P 〈 0. 01 ) and day 45 (87. 7%±4. 6% vs 78.3%±2.4%, t = 4. 403, P 〈 0. 01 ) in PSD animals. There was a statistically significant increased proportion of BrdU-positive cells co-stained with GFAP in PSD animals compared with the ischemia ones on day 30 and 45 ( t = 4. 226, 8. 945, both P 〈 0. 01 ). Conclusion CMS following ischemia exerts an inhibitory effect on hippocampal survival of new born cells as well as their differentiation into neurons, while promotes new born cells differentiating into astrocytes.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2008年第9期614-617,共4页
Chinese Journal of Neurology
基金
国家自然科学基金资助项目(30570656,30600206)
江苏省自然科学基金重点项目(BK2006708)
关键词
脑血管意外
抑郁症
海马
细胞增殖
细胞存活
细胞分化
Cerebrovascular accident
Depressive disorder
Hippocampus
Cell proliferation
Cell survival
Cell differentiation