Diabetic Microangiopathy: Impact of Impaired Cerebral Vasoreactivity and Delayed Angiogenesis After Permanent Middle Cerebral Artery Occlusion on Stroke Damage and Cerebral Repair in Mice

• DOI: 10.2337/db14-0759
• Publication Date: 2014-10-07T07:23:08Z
• Authors: Marine Poittevin; Philippe Bonnin; Cynthia Pimpie; Léa Rivière; Catherine Sebrié; Anthony Dohan; Marc Pocard; Christiane Charri...; Nathalie Kubis
• Keywords: Penumbra; Microangiopathy; Extravasation; NeuN

Diabetes increases the risk of stroke by three, related mortality, and delays recovery. We aimed to characterize functional structural alterations in cerebral microvasculature before after experimental ischemia a mouse model type 1 diabetes. hypothesized that preexisting brain microvascular disease patients with diabetes might partly explain increased severity impact on outcome. was induced 4-week-old C57Bl/6J mice intraperitoneal injections streptozotocin (60 mg/kg). After 8 weeks diabetes, vasoreactivity neurovascular network CO2 abolished not reversed nitric oxide (NO) donor administration; endothelial NO synthase (eNOS) neuronal (nNOS) mRNA, phospho-eNOS protein, nNOS, phospho-nNOS protein were significantly decreased; angiogenic vessel maturation factors (vascular growth factor [VEGFa], angiopoietin (Ang1), Ang2, transforming factor-β [TGF-β], platelet-derived [PDGF-β]) blood-brain barrier (BBB) occludin zona occludens (ZO-1) expression microvessel density without changes ultrastructural imaging. permanent focal induction, infarct volume neurological deficit at D1 D7, death (TUNEL+/NeuN+ cells) BBB permeability (extravasation Evans blue) D1. At CD31+/Ki67+ double-immunolabeled cells VEGFa Ang2 increased, indicating delayed angiogenesis. show microangiopathy thus explains