脑梗死大鼠原位神经干细胞的增殖和分化

Proliferation and Differentiation of Endogenous Neuronal Stem Cells in situ in the Ischemic Adult Rat Brain

目的研究成年大鼠脑梗死后原位神经干细胞的增殖和分化。方法运用BrdU标记法检测脑局灶梗死大鼠侧脑室下区(SVZ)与海马齿状回颗粒细胞层下区(SGZ)原位神经干细胞的增殖情况,运用荧光双标法检测其分化的细胞表型。结果SVZ BrdU+细胞数量于脑梗死后1 d开始升高(P<0.01),而SGZ BrdU+细胞则于梗死后4 d开始升高。SVZ与SGZ BrdU+细胞均于7 d达到高峰(P<0.01),14 d开始下降(P<0.01),至28 d后与对照组差异无显著性意义(P>0.05)。半定量显示脑梗死7 d后,SVZ与SGZ BrdU+细胞数分别较假手术组升高5倍和8倍。对原位神经干细胞分化的研究发现,脑梗死后35 d在梗死侧大脑半球,BrdU+细胞总数中约(73.5±15.7)%表达神经元细胞表型NeuN,(37.6±9.9)%表达胶质细胞表型GFAP。结论大鼠脑梗死能刺激原位神经干细胞的增殖并促进了神经再生。

Objective To investigate the proliferation and differentiation of neuronal progenitor cells in the rat brain after cerebral ischernia. Methods Brornodeoxyuridine （BrdU） labeling method was used to identify the proliferation of neuronal stern cells in the SGL and SVZ and double-irnrnunostaining with confocal microscopy to determine the cell phenotype. Results The number of BrdU positive cells in the SVZ began Io increase one day after ischernia （P〈0.01）. but in the SGZ these cells started to increase 4 days after ischemia （P〈0.01）. Both in the SVZ and SGZ. the BrdU-positive cells reached the peak 7 days after ischernia （P〈0.01 ）. began to decrease 14 days after ischernia （P〈0.01） and declined to lhe level of sham rats 28 days after ischernia （P〉0.05）. Serni-quantitative analysis revealed that compared with the sham group, the BrdU-positive cells were increased 5 folds in SVZ and 8 folds in SGZ respectively 7 days after ischernia. Double-irnmunoslaining ,showed that of all BrdUpositive cells in ischernic hemisphere, about （73.5± 15.7） % expressed the neuronal phenotype NeuN and （37.6±9.9） % expressed glia phenotype GFAP 35 days after ischernia. Conclusion Ischernic stress stimulated the proliferation of endogenous neuronal progenitor cells and enhanced neurogenesis after brain injury.