ABSTRACT
AIM: To explored the potential role of HIF-1α in reducing the neuronal apoptosis and promoting the neuronal proliferation after stroke in rats. METHODS: The bone marrow-derived mesenchymal stem cells (BMSCs) were lentivirally transduced to express the stable form of HIF-1α. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. Neurological function was evaluated by modified neurological severity score (mNSS). Cerebral infarct volume was measured by TTC staining. Immunohistochemistry and terminal deoxynucleotidyltransferase mediated dUTP nick end labeling (TUNEL) method were performed to detect neuronal proliferation and apoptosis. RESULTS: Significant improvement of neurological deficits was found in BMSCs-mHIF-1α rats as compared to the control animals at 14th d and 28th d after MCAO (P<0.05). Significant reduction of infarct volume was observed in rats in BMSCs-mHIF-1α group at 3rd day after MCAO (P<0.05). Histological evaluation showed that BMSCs-mHIF-1α treatment significantly promoted neuronal survival and proliferation in the ischemic boundary area. CONCLUSION: Constitutive expression of HIF-1α in BMSCs reduces the neuronal apoptosis and promotes the neuronal proliferation after stroke in rats.
ABSTRACT
Hypoxia-inducible factor-1 (HIF-1), as a nuclear transcription regulator of the hypoxic response, is up-regulated during hypoxia, and it regulates a series of downstream target gene expression, such as vascular endothelial growth factor, glucose transporter and erythropoietin through binding with hypoxia response element. It plays important roles in angiogenesis, anerobic metabolism, cell survival, proliferation, migration, and differentiation.This article reviews the structure, function and activity regulation of HIF-1 and its roles in acute ischemic brain injury.
ABSTRACT
AIM:To explored the potential role of HIF-1? in reducing the neuronal apoptosis and promoting the neuronal proliferation after stroke in rats. METHODS:The bone marrow-derived mesenchymal stem cells (BMSCs) were lentivirally transduced to express the stable form of HIF-1?. Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. Neurological function was evaluated by modified neurological severity score (mNSS). Cerebral infarct volume was measured by TTC staining. Immunohistochemistry and terminal deoxynucleotidyltransferase mediated dUTP nick end labeling (TUNEL) method were performed to detect neuronal proliferation and apoptosis. RESULTS:Significant improvement of neurological deficits was found in BMSCs-mHIF-1? rats as compared to the control animals at 14th d and 28th d after MCAO (P