Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI, 48202, USA.
J Neurol Sci. 2010 Jul 15;294(1-2):107-11. doi: 10.1016/j.jns.2010.03.020. Epub 2010 May 7.
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 NGR and reduced activated microglia may contribute to functional recovery after stroke.
在这项研究中，我们研究了用烟酸（维生素 B3）的缓释制剂尼可司他（Niaspan）和降胆固醇药物辛伐他汀联合治疗实验性中风对大鼠缺血性脑内功能结果、轴突损伤、轴突密度和 Iba-1 免疫反应性小胶质细胞表达的影响。成年雄性大鼠接受 2 小时大脑中动脉闭塞（MCAo），并在 MCAo 后 24 小时开始单独用尼可司他、辛伐他汀或联合尼可司他和辛伐他汀治疗，每天治疗 14 天。进行神经功能测试。通过 APP 和 Bielschowsky 银分别评估轴突损伤和密度。还测量了缺血性脑中的 Nogo66 受体（NgR）表达和免疫反应性小胶质细胞（Iba-1）。与 MCAo 对照组相比，尼可司他和辛伐他汀单药治疗和联合治疗显著促进中风后的功能结果（p<0.05）。与尼可司他或辛伐他汀单药治疗组相比，尼可司他和辛伐他汀联合治疗诱导了附加但非协同作用。联合治疗显著降低 APP 表达并增加 Bielschowsky 银表达。缺血性脑内的 NgR 和 Iba-1 表达显著降低。这些数据表明，用尼可司他和辛伐他汀联合治疗实验性中风可显著改善功能结果，减少轴突损伤并增加轴突密度。NGR 和激活的小胶质细胞表达的减少可能有助于中风后的功能恢复。
