While neuroprotective therapies that up regulate HIF-1α activity have been reported to promote pro-angiogenic responses and improve stroke outcome in diabetic mice [26], several reports also indicate that DM up regulates HIF-1α protein levels and increases HIF-1α transcriptional activity in endothelial cells, which in turn can adversely affect tight junction proteins and BBB permeability [27, 28]. This evidence concerns the gene HIF1A and stroke disorder.