Bone marrow stromal cells enhance the angiogenesis in ischaemic cortex after stroke: involvement of notch signalling.

Angiogenesis takes place after brain ischaemia, and stroke-induced angiogenesis in ischaemic brain may be associated with improved neurological recovery. Bone MSCs (marrow stromal cells) transplantation can promote this vital angiogenesis in ischaemic zones, but the mechanisms by which MSCs promoting angiogenesis are unclear. The Notch signalling pathway may play an important role in embryonic blood vessels development and tumour angiogenesis, but whether it is also involved in angiogenesis after cerebral ischaemia is uncertain. We therefore investigated the Notch signalling pathway in angiogenesis after stroke. Rats were subjected to MCAo (middle cerebral artery occlusion) and treated intravenously with or without MSCs at 24 h after injury. On day 1, 3 and 7 after treatment with MSCs or PBS, immunofluorescent staining, Western blot and RT-PCR (reverse transcription-PCR) assays were carried out to evaluate angiogenesis, and expression of VEGF (vascular endothelial growth factor) and Notch signals in the ischaemic cortex. Immunofluorescent showed a significant increase in both new microvessels, VEGF-positive cells and Notch1-positive microvessels in the ischaemic cortex in MSCs-treated group. RT-PCR indicated that MSC transplantation significantly raised VEGF mRNA and Hes1 mRNA levels in the ischaemic cortex. The data suggest that treatment with MSCs enhances stroke-induced angiogenesis in ischaemic brain, and that the Notch signalling pathway is involved.