| Background and objective: Previous studies have reported that braindamage causes neurogenesis in the central nervous system. Neurogenesisoccurs in the adult mammals brain subventricular zone (SVZ) of the lateralventricle and the subgrandular zone(SGZ) of the hippocampal dentategyrus. Neural stem cells(NSCs) in the adult SVZ and SGZ can be activated,proliferate and migrate to ischemic penumbra and then promoteneurological rehabilitation, but the mechanism of proliferation,differentiation, immigration and integration for neural stem cells is notclear. Sonic Hedgehog(Shh) signaling pathway is central to thedevelopment and patterning of the nervous system and other organs. Inrecent years, the Shh signaling pathway has received much concern dueto the close relationship with the formation of nervous tissue and theproliferation, differentiation, and migration of neural stem cells. However,whether the Shh signaling pathway is involved in the proliferation,differentiation, and migration of neural stem cells after cerebral ischemia is not clear. This study was to observe the expression of the Shh signalingpathway components in the SVZ and SGZ of focal cerebral ischemic rats,and then explore whether or not Shh signaling pathway participate inregulation of neurogenesis after cerebral ischemic stroke in rats.Methods:84SD rats were divided into normal control group, shamoperation group, experimental group at6h,12h,24h,3d,7d (n=12for timepoint) after focal cerebral ischemia. Experimental group was made byfilament occlusion of right middle cerebral artery. RT-PCR,Immunohistochemistry and Western blotting were used to detect themRNA and protein levels of Shh and Gli1in the SVZ and SGZ.Result: In the SVZ, there were expressions of Shh and Gli1proteinand mRNA, but were not significant difference in the normal control andsham operation group (P>0.05). The protein and mRNA expressions of Shhand Gli1were increased significantly at6h (P<0.01), peaked at24h, anddropped to normal levels at3days (P>0.05) and increased significantly at7days (P<0.01) in experimental group. In the SGZ, compared with thenormal control group, the protein and mRNA expressions of Shh and Gli1in the sham operation were also no significant difference (P>0.05). Theprotein and mRNA expressions of Shh and Gli1were increasedsignificantly at6h (P<0.01), peaked at24h, and increased slightly at3daysafter ischemia (P<0.05)and increased significantly at7days (P<0.01) inexperimental group detected by RT-PCR and Werstern blot, but dropped to normal levels at3days detected by Immunohistochemistry(P>0.05).Conclusion:(1) There were expression of Shh and Gli1protein andmRNA in the SVZ and SGZ of normal adult rats.(2) Permanent focal cerebal ischemia unregulated the expression ofShh and Gli1in the SVZ and SGZ of rats. The pattern of dynamicexpression for Shh signaling was concord with the pattern ofneurogenesis in the SVZ and SGZ.(3) Shh signaling pathway may participate in regulation ofneurogenesis after cerebral ischemic stroke in rats. |
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