Intravenously administered BMSCs reduce neuronal apoptosis and promote neuronal proliferation through the release of VEGF after stroke in rats

Abstract

Background: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate neurological deficits after stroke in the rodent.Objective: The purpose of this study was to investigate the potential mechanisms underlying the neuroprotective effects of implanted BMSCs.Methods: Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAo) in Sprague-Dawley rats. BMSCs were intravenously transplanted at 24 hours after MCAo. Neurological function was evaluated using modified neurological severity score and Morris water maze test. Immunohistochemistry and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining were performed to detect neuronal apoptosis and proliferation. The protein and mRNA levels of vascular endothelial growth factor (VEGF) were determined by ELISA and reverse transcriptase polymerase chain reaction, respectively.Results: Significant improvement of neurological deficits was found in BMSC-treated rats compared with control animals at 14 and 28 days after MCAo (p<0·05). Histological evaluation showed that BMSCs treatment significantly promoted neuronal survival and proliferation in the ischemic boundary area. The expression of VEGF was predominantly increased in the ischemic hemisphere of BMSC-treated rats compared with the other groups. On the other hand, transduction of VEGF RNAi lentivirus partially attenuated the above described beneficial effects of systemically administered BMSCs.Conclusion: Our data suggest that intravenously administrated BMSCs facilitate neurological function, reduce neuronal apoptosis and promote neuronal proliferation through the release of VEGF.