Niaspan Increases Axonal Remodeling After Stroke In Type1Diabetes Rats

Objective:We investigated axonal plasticity in the bilateral motor cortices and the long term therapeutic effect of Niaspan on axonal remodeling after stroke in type-1diabetic (T1DM) rats.Methods:T1DM was induced in young adult male Wistar rats via injection of streptozotocin. T1DM rats were subjected to2h transient middle cerebral artery occlusion (MCAo) and were treated with40mg/kg Niaspan or saline starting24h after MCAo daily for28days. Anterograde tracing using biotinylated dextran amine (BDA) injected into the contralateral motor cortex was performed to assess axonal sprouting in the ipsilateral motor cortex area. Functional outcome, SMI-31(a pan-axonal microfilament marker), Bielshowsky silver and Synaptophysin expression were measured.Results:Niaspan treatment of stroke in TIDM-MCAo rats significantly improved functional outcome after stroke and increased SMI-31, Bielshowsky silver and Synaptophysin expression in the ischemic brain compared to saline treated TIDM-MCAo rats (p<0.05). Using BDA to anterograde label axons and terminals, Niaspan treatment significantly increased axonal density in ipsilateral motor cortex in TIDM-MCAo rats (p<0.05. n=7/group). Using a Primary cortical neuron (PCN) culture, Niacin treatment of PCN significantly increased Ang1expression under high glucose condition. Niacin and Ang1significantly increased neurite outgrowth, and Anti-Angl antibody marginally attenuated Niacin induced neurite outgrowth (p=0.06, n=6/group) in cultured PCN under high glucose condition.Conclusion:Niaspan treatment increased ischemic brain Ang1expression and promoted axonal remodeling in the ischemic brain as well as improved functional outcome after stroke. Ang1may partially contribute to Niaspan-induced axonal remodeling after stroke in T1DM-rats.