Combination treatment of experimental stroke with Niaspan and Simvastatin, reduces axonal damage and improves functional outcome.

Combination treatment of experimental stroke with Niaspan and Simvastatin, reduces axonal damage and improves functional outcome.
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DOI:
10.1016/j.jns.2010.03.020
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发表时间:
2010-07-15
影响因子:
4.4
通讯作者:
Chopp, Michael
Chopp, Michael
中科院分区:
医学3区
文献类型:
--
作者:
Shehadah, Amjad;Chen, Jieli;Cui, Xu;Roberts, Cynthia;Lu, Mei;Chopp, Michael

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在本研究中,我们观察了烟酸(维生素B3)缓释剂Niaspan和降胆固醇药物辛伐他汀联合治疗实验性卒中对大鼠脑缺血后功能结局、轴突损伤、轴突密度和Iba-1免疫反应阳性小胶质细胞表达的影响。成年雄性大鼠大脑中动脉闭塞(MCAO)2 h后,分别给予或不给予Niaspan、辛伐他汀及Niaspan和辛伐他汀联合治疗。进行神经功能测试。用淀粉样前体蛋白(APP)和Bielschowsky银染色法评价轴突损伤程度和密度。同时检测缺血脑组织中Nogo66受体(NGR)的表达和小胶质细胞(Iba-1)的免疫反应。与MCAO对照组动物相比,NIASPAN和辛伐他汀单独治疗和联合治疗显著改善了卒中后的功能结果(P<0.05)。而与奈斯潘或辛伐他汀单独治疗相比,奈斯潘和辛伐他汀联合治疗可诱导相加作用,但不能产生协同作用。联合治疗显著降低APP表达,增加Bielschowsky银蛋白表达。缺血脑组织NGR和Iba-1表达明显降低。这些数据表明,尼卡潘和辛伐他汀联合治疗实验性卒中可显著改善功能结局,减少轴突损伤,增加轴突密度。神经生长因子受体表达减少和激活的小胶质细胞减少可能有助于卒中后功能的恢复。
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 hours middle cerebral artery occlusion (MCAo) and treated with or without Niaspan alone, Simvastatin alone and combination Niaspan and Simvastatin starting 24 hours after MCAo and daily for 14 days. Neurological functional tests were performed. Axonal damage and density were evaluated by Amyloid Precursor Protein (APP), 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 promotes functional outcome after stroke (p<0.05) compared to MCAo control animals. While 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.
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