Autologous transplantation of adipose-derived mesenchymal stem cells attenuates cerebral ischemia and reperfusion injury through suppressing apoptosis and inducible nitric oxide synthase

Abstract

The purpose of this study was to investigate whether autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) has a neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury in rats and to explore the possible underlying mechanisms. Adult male Sprague-Dawley rats were randomly assigned into the sham, I/R injury model (I/R), and model plus autologous transplantation of ADMSCs (ADMSC) groups. Cerebral I/R injury was induced by 2 h middle cerebral artery occlusion (MCAO) followed by reperfusion for 24 h. Rats in the I/R and ADMSC groups were intravenously injected with culture medium and ADMSCs (2.0x10(6)), respectively, at the onset of reperfusion and 12 h after reperfusion. Cerebral infarct volume was detected by triphenyltetrazolium chloride (TTC) staining. The histopathological changes and neuronal apoptosis in the ischemic penumbra were evaluated with H&E staining and the TUNEL assay, respectively. The nitric oxide (NO) content, caspase-3 activity and the Bax/Bcl-2 protein ratio were also measured. Moreover, the inducible nitric oxide synthase (iNOS) expression in the ischemic regions of rats was determined by immunohistochemical staining, quantitative real-time RT-PCR and western blot analysis. We found that autologous transplantation of ADMSCs significantly reduced the cerebral infarct volume, improved the I/R injury-induced brain damages and inhibited the neuronal apoptosis. ADMSC implantation also decreased caspase-3 activity and the Bax/Bcl-2 protein ratio, and markedly downregulated the expression of iNOS and thus prevented NO release in response to cerebral I/R injury. Taken together, our results demonstrated that autologous transplantation of ADMSCs can protect the brain against cerebral I/R injury via the inhibition of neuronal apoptosis and iNOS expression.