Niaspan increases axonal remodeling after stroke in type 1 diabetes rats.

Abstract

BACKGROUND AND 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-1 diabetic (T1DM) rats.

EXPERIMENTAL APPROACHES:

T1DM was induced in young adult male Wistar rats via injection of streptozotocin. T1DM rats were subjected to 2h transient middle cerebral artery occlusion (MCAo) and were treated with 40 mg/kg Niaspan or saline starting 24 h after MCAo and daily for 28 days. 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), Bielschowsky silver and synaptophysin expression were measured. In vitro studies using primary cortical neuron (PCN) cultures and in vivo BDA injection into the brain to anterogradely label axons and terminals were employed.

RESULTS:

Niaspan treatment of stroke in T1DM-MCAo rats significantly improved functional outcome after stroke and increased SMI-31, Bielschowsky silver and synaptophysin expression in the ischemic brain compared to saline treated T1DM-MCAo rats (p<0.05). Using BDA to anterograde label axons and terminals, Niaspan treatment significantly increased axonal density in ipsilateral motor cortex in T1DM-MCAo rats (p<0.05, n=7/group). Niacin treatment of PCN significantly increased Ang1 expression under high glucose condition. Niacin and Ang1 significantly increased neurite outgrowth, and anti-Ang1 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 Ang1 expression and promoted axonal remodeling in the ischemic brain as well as improved functional outcome after stroke. Ang1 may partially contribute to Niaspan-induced axonal remodeling after stroke in T1DM-rats.

• Authors: Tao Yan, Michael Chopp, Xinchun Ye, Zhongwu Liu, Alex Zacharek, Yisheng Cui, Cynthia Roberts, Ben Buller, Jieli Chen
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 46 Issue 1 Pg. 157-64 (Apr 2012) ISSN: 1095-953X [Electronic] United States
• PMID: 22266016 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Vitamin B Complex
• Niacin

Topics

• Animals
• Axons (drug effects, physiology)
• Diabetes Mellitus, Type 1 (complications, physiopathology)
• Disease Models, Animal
• Female
• Infarction, Middle Cerebral Artery (complications, drug therapy, pathology)
• Male
• Neuronal Plasticity (drug effects, physiology)
• Niacin (analogs & derivatives, pharmacology)
• Pregnancy
• Primary Cell Culture
• Rats
• Rats, Wistar
• Vitamin B Complex (pharmacology)