目的：探讨创伤性脑损伤后脑室下区（SVZ）神经干细胞（NSCs）的增殖分化的时程变化。方法采用随机数字表法将大鼠分为3组，对照组不做任何处理，假手术组仅切开头皮和颅骨开窗，实验组采用Feeney氏法造成颅脑损伤（TBI）。选用Nestin与BrdU两种细胞标志物及神经元特异标志物神经元特异性烯醇化酶（NSE）及胶质细胞标志物GFAP，采用免疫荧光化学方法对3组脑组织标本分别行双标蛋白抗体免疫荧光染色，检测TBI后SVZ内源性NSCs的增殖、分化变化。结果 TBI后，伤侧SVZNestin/NSE、Nestin/GFAP、BrdU/NSE、BrdU/GFAP标记阳性细胞均明显增多，伤后第1天开始升高，第3天达峰值，第14天恢复正常，实验组4个时间点间及实验组与对照组对应时间点间的比较差异均有显著性意义，其中以Nestin/GFAP标记的增殖分裂阳性细胞升高最显著。结论 TBI后，动员了伤侧SVZ中的NSCs，诱导该区内源性NSCs的增殖分化，提示SVZ是NSCs增殖分化的重要的生发中心之一。%Objective To observe the time course of proliferation and differentiation of neural stem cells (NSCs) in the subventricular zone (SVZ) of rats following traumatic craniocerebral injury (TBI). Methods Forty-eight SD rats were randomized into 3 groups, namely the control group without any treatment, the sham-operated group with scalp incision and preparation of a cranial window, and TBI group with craniocerebral injury induced by Feeney's method. With nestin and BrdU as two cell markers, NSE as the neuron-specific marker and GFAP as the glial cell marker, immunofluorescence assay with double labeled antibodies was performed to examine the proliferation and differentiation of endogenous NSCs in the SVZ at different time points after TBI. Results The numbers of cells positive for nestin/NSE, nestin/GFAP, BrdU/NSE, and BrdU/GFAP in the SVZ of the rats increased significantly after TBI. The positive cells began to increase at 1 day after TBI, reached the peak level at day 3 and became normal at day 14, showing significant differences between the time points of measurement following TBI and from the cell numbers in the control group measured at the same time points. The cells positive for nestin/GFAP showed the most distinct increase in the SVZ of the rats with TBI. Conclusion TBI results in mobilization of the NSCs in the SVZ on the injured side to cause the proliferation and differentiation of the endogenous NSCs. The SVZ is one of the most important germinal centers of NSC proliferation and differentiation.
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