Vegf Increase The Expression Of Noggin To Promote Within The Striatum After Cerebral Ischemia Neurogenesis

It is well known that neurogenesis is restricted in the subventricular zone(SVZ) and hippocampal dentate gyrus(DG) throughtout adulthood of mammalian brains in physiological conditions.Neurogenesis in the striatum and cerebral cortex can be stimulated by brain stroke,which provides a potentially significant therapeutic strategy for ischemic injury.However,the number of newborn neurons is very limitted.Therefore,attention should be given to study how to promote migration,proliferation and differentiation of neural progenitor cells(NPCs).Vascular endothelial growth factor(VEGF),an angiogenic and neurotrophic/neuroprotective factor,is now recognized to enhance cell proliferation in the SVZ and DG under physiological conditions.In addition,VEGF overexpression enhances striatal neurogenesis in brain of adult rat after a transient middle cerebral artery occlusion.To investigate the molecular mechanism how VEGF overexpression promotes ischemia-induced neurogenesis in rat brain,we intraventricularly injected human VEGF-expressive plasmid(phVEGF) or control plasmid(pEGFP) and Noggin antisense into rat brains after middle cerebral artery occlusion(MCAO).Double immunohistochemical staining was used to detect newborn cells in ischemic striatum. Western blot was used to probe the expression of BMP4,Noggin andβ-catenin in the ischemic striatum.The results were summarized as follows:1.VEGF overexpression up-regulated the expression of Noggin in the ischemic striatum at 3 days after MCAO.To observe the effect of VEGF overexpression on the expression of Noggin,BMP4 and P-catenin in the ischemic striatum,we intraventricularly injected VEGF expressing or control plasmid into the lateral ventricle after ischemia.VEGF overexpression significantly up-regulated the expression of Noggin,but not BMP4 orβ-catenin,in the ischemic striatum at 3 days after MCAO.These results suggested that VEGF overexpression might increase neurogenesis via Noggin in the ischemic striatum.2.Noggin antisense knock-down Noggin expression in the ischemia-injured striatum at 3 days after MCAO.To measure the effect of Noggin on VEGF overexpression-induced neurogenesis in ischemic striatum,we intraventricularly injected Noggin antisense to inhibit Noggin expression in the ischemia-injured striatum.We observed that Noggin antisense decreased Noggin expression in the striatum of adult rats at 3 days following MCAO in the groups of phVEGF or control plasmid treatment.3.Noggin antisense counteracted the effect of VEGF overexpression-induced neurogenesis in the ischemic striatum.To measure the effect of Noggin antisense on VEGF-induced neurogenesis in ischemic rat brain,we injected VEGF overexpression plasmid and/or Noggin antisense into the lateral ventricle after ischemic operation.Our results showed that Noggin antisense administration decreased VEGF-induced increase of BrdU~+-NeuN~+ cells in the ipsilateral ischemic striatum at 28 days after MCAO.Interestly,the BrdU~+-GFAP~+cells were significantly increased at the same time point.These findings suggested that Noggin antisense counteracted the effect of VEGF overexpression-induced neurogenesis in the ischemic striatum.Conclusion:VEGF increases striatal neurogenesis via upregulating Noggin in the ischemia-injured brain.