Activation of PPARβ/δ by DHA induces VEGF-A expression to promote angiogenesis in the cerebral ischemia penumbra

Abstract The ischemia penumbra is an area of brain tissue where is damaged but not yet dead after ischemic stroke,it has the potential for functional recovery provided if local blood flow can be reestablished.Docosahexaenoic acid (DHA) is protective after experimental ischemic stroke.To explore DHA promote angiogenesis underlying mechanisms of angiogenesis in the cerebral ischemia penumbra, Male Sprague-Dawley rats underwent 2h of middle cerebral artery occlusion (MCAo) and treated with DHA (5mg/kg, IV) 1h after.Neuro-behavioral assessments and 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to assess the cerebral infarction volume on hours 6, 12, 24,48 and 72, PPARβ/δ、VEGF-A、VEGFR2 and P-VEGFR2 expression were measured by Western blotting、brain tissue expressions of TNF-α, IL-1β and NF-κB were assessed using ELISA, NeuN、CD31、α-sma cells in the ischemia penumbra were analyzed using immunofluorescenceon hour 72 after onset of stroke. Post-treatment with DHA ameliorated neurological defects, diminished cerebral infarction volume, enhanced neuronal survival, downregulated inflammation、promoted the expression of angiogenesis related proteins and protected ischemic penumbra by increasing CD31、α-sma cells and vessels .On the contrary, this promote angiogenesis in the cerebral ischemia penumbraprotective effect was reversed after DHA cotreatment with GSK0660, a selective antagonist of the PPARβ/δ.Finally, our experiment clearly demonstrating DHA protect the rat cerebral ischemic injury (MCAO) model, more importantly, DHA was first demonstrated to promote ischemic penumbra angiogenesis through the PPARβ/δ pathway.