Angiogenesis and neural progenitor proliferation induced by intracarotid administration of mesenchymal stem cells in rats with cerebral ischemia

To investigate the mechanisms of bone marrow mesenchymal stem cells (MSCs) transplantation on neurological function following focal cerebral ischemia in rats.Methods Forty Sprague-Dawley rats, subjected to middle cerebral artery occlusion (MCAo) for 2 hours by intraluminal vascular occlusion, were divided into MSC transplantation group (TG) and cerebral ischemia control groups (CG) at random. MSCs were administrated via carotid artery at 24 hours after MCAo in T groups. At 1, 2, 4 and 12 weeks after MCAo, rats were killed in batches to investigate dynamically the regeneration of microvessels and proliferation of neuronal progenitors in ischemic region by immunohistochemistry and in situ hybridization.Results ①Notable microvessel proliferation in the injured cortex was found 1 week after MCAo and peaked at 2 weeks, then decreased at 4 and 12 weeks. The microvessel density (MVD) in the focal cortex of rats treated with MSC was significantly higher than that of C groups at 1,2,4 and 12 weeks after MCAo (P0.05). Plenty of VEGFmRNA positive signals were found in cortical and perivascular neurons at 1 and 2 weeks after MCAo, and were more intensive in the T groups than those in C groups at 4 and 12 weeks after MCAo. ②At 1 week after MCAo, numerous nestin -positive cells (NPC) in the injured cortex of parietal lobe, caudate putamen, ependyma ,subependymal zone were observed and the NPC count showed the greatest amount of positive cells at the first week after MCAo, decreased at 2 weeks; and at 12 weeks after MCAo, only scanty NPC scattered in the focal cortex of C groups, whereas, in the T groups, the amount of positive cells remained great.The NPC amount of T groups at each time interval was significantly higher than that of C group(P0.05) . ③At 1 week after MCAo, large amounts BrdU-labeled cells in the ischemic cortex, caudate putamen, ependyma ,subependymal zone were seen and positive-cell count appeared highest at the first week after MCAo, decreased after 2 weeks; and at 4 and 12 weeks , only scanty BrdU positive cells scattered in the focal cortex of C groups, while, in T groups, a number of positive cells could still be seen in the focal cortex.The BrdU positive cell count of the T group was significantly higher than that of the C group at each time interval(P0.05).Conclusion These results suggest that MSC transplantation can improve neurological function in cerebral ischemic rats through promoting revascularization and proliferation of neuronal progenitors in the injured region.