期刊
JOURNAL OF THE NEUROLOGICAL SCIENCES
卷 294, 期 1-2, 页码 107-111出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jns.2010.03.020
关键词
Niaspan; Simvastatin; Axonal damage; Microglia; Nogo receptor; Stroke
资金
- National Institute on Aging [RO1 AG031811]
- National Institute of Neurological Diseases and Stroke [PO1 NS23393, 1R41NS064708]
- American Heart Association [09GRNT2300151]
In this study we examined the effect of combination treatment of experimental stroke with Niaspan, a prolonged-release formulation of Niacin (vitamin B3), and Simvastatin, a cholesterol-lowering drug, on functional outcome, axonal damage, axonal density and the of Iba-1 immunoreactive microglia expression in the ischemic brain of rats. Adult male rats were subjected to 2 h middle cerebral artery occlusion (MCAo) and treated with or without Niaspan alone, Simvastatin alone and combination Niaspan and Simvastatin starting 24 h after MCAo and daily for 14 days. Neurological functional tests were performed. Axonal damage and density were evaluated by Amyloid Precursor Protein (APP) and Bielschowsky silver, respectively. Nogo66 Receptor (NgR) expression and immunoreactive microglia (Iba-1) were also measured in the ischemic brain. Niaspan and Simvastatin monotherapy and combination treatment significantly promote functional outcome after stroke (p<0.05) compared to MCAo control animals. Combination treatment with Niaspan and Simvastatin induces additive but not synergetic effects when compared to Niaspan or Simvastatin monotherapy groups. Combination treatment significantly decreased APP expression and increased Bielschowsky silver expression. NGR and Iba-1 expression were significantly decreased in the ischemic brain. These data suggest that treatment of experimental stroke with combination of Niaspan and Simvastatin significantly improves functional outcome, reduces axonal damage and increases axonal density. Decreased expression of the NCR and reduced activated microglia may contribute to functional recovery after stroke. (C) 2010 Elsevier B.V. All rights reserved.
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