Neurorestorative Effect Of Niaspan On Type1Diatbetic Rats After Stroke

Introduction:We investigated the changes and the molecular mechanisms of cerebral vascular damage and tested the therapeutic effects of Niaspan in type-1streptozotocin induced diabetic (T1DM) rats after stroke.Methods:T1DM-rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated without or with Niaspan. Non-streptozotocin rats (WT) were also subjected to MCAo. Functional outcome, blood-brain-barrier (BBB) leakage, microvascular patency, immunostaining and in vitro arterial explant cell culture were performed.Results:Compared to WT-MCAo-rats, T1DM-MCAo-rats did not show an increase lesion volume, but exhibited significantly increased brain hemorrhage, BBB leakage and vascular damage as well as decreased microvascular patency and functional outcome after stroke. Niaspan treatment of stroke in T1DM-MCAo-rats significantly increased microvascular patency, attenuated BBB damage, promoted vascular remodeling and improved functional outcome after stroke. T1DM-MCAo-rats exhibited significantly increased Angiopoietin2(Ang2) expression, but decreased Angl expression in the ischemic brain compared to WT-MCAo-rats. Niaspan treatment attenuated Ang2, but increased Angl expression in the ischemic brain in T1DM-MCAo-rats. In vitro data show that arterial explant cell migration significantly decreased in arteries derived from T1DM-MCAo-rats compared to arteries from WT-MCAo-rats. Niacin and Angl treatment increased arterial explant cell migration in T1DM-artery. Anti-Angl significantly attenuated Niacin-induced arterial cell migration.Conclusions:Niaspan treatment of stroke in T1DM-rats promotes vascular remodeling and improves functional outcome. The Angl/Ang2pathway may contribute to Niaspan induced brain plasticity. Niaspan warrants further investigation as a therapeutic agent for the treatment of stroke in diabetics.