Neurogenesis In The Dentate Gyms After Global Ischemia Reperfusion

Ischemic stroke is one of the commonest neurological diseases with relative high lethality and disabled rate. People have been trying to seek for efficient treatments for many years, but until now, there has been no breakthrough. Recently, a series of experiments suggested that ongoing neurogenesis hi the dentate gyms not only occurred in the normal adult mammalian brains, but also was enhanced by many physiological activities and pathological events. These findings provide possibility and feasibility for reconstructing cerebral infarct region, and will bring a new bright clue for treating cerebral vascular diseases.In this study, we try to investigate the temporal profile of neurogenesis in the dentate gyrus after global ischemia reperfusion, and to explore the possible mechanisms related to neurogenesis by using male mature Sprague-Dawley subjected to 4-vessel occlusion(4-VO) model, and systemic BrdU to label dividing cells. Firstly, we investigated the regularity of neurogenesis in thedividing cells. Firstly, we investigated the regularity of neurogenesis in the dentate gyrus after global reperfusion 3d^ lw> 2w\ 3w. Secondly, we observed the effects of Glu receptor blocker (MK-801 and DNQX) on neurogenesis in the dentate gyrus after cerebral ischemia, and discussed the role of Glu in enhanced neurogenesis. Lastly, we investigated the influence of bFGF on neurogenesis in the dentate gyrus after global reperfusion. Our results showed:(1) Quantitative analysis of BrdU labeling revealed a significant increase of the proliferation rate of neural precursor cells in the dentate gyrus 7 and!4d after global ischemia reperfusion compared with controls(P <0.01). The number of BrdU labeled cells in the dentate gyrus returned to baseline levels by 2Id after cerebral ischemia.Most of newborn cells migrated into the granule cell layer from the SGZ,displayed neuronal phenotype.(2) MK-801 (Img/kg i.p.) significantly reduced the number of BrdU labeled cells in the dentate gyrus 7 and 14d after global ischemia reperfusion(P <0.01),and inhibited proliferation rate of neural precursor cells in the dentate gyrus. DNQX injected(15mg/Kg i.p.) 30min before global ischemia reperfusion did not infuence the number of BrdU labeled cells in the dentate gyrus at the 7th d and 14th d after ischemia.(3) bFGF injected in lateral ventricle significantly inhanced the number of BrdU labeled cells in the dentate gyrus at 7th d after global ischemia reperfusion (P<0.01), but did not influence the proliferation rate of neural precursor cells in the dentate gyrus 14d after global ischemia reperfusion.Our results demonstrate:(1) Neuron proliferation in the dentate gyrus was enchanced during a time6window (3-14d) after cerebral ischemia.Its mechanisms may be related to the changes of microenvironment, neurotrans mitters, neurotrophic factors in the dentate gyms following ischemia.(2) The activation of Glu-NMDAR pathway after global ischemia reperfusion can promote the neurogenesis in the dentate gyms.(3) Exogenous bFGF could enhance the neurogenesis in the dentate gyrus after global ischemia reperfusion.