Yrjänheikki Juha, Koistinaho Jari, Kettunen Mikko, Kauppinen Risto A, Appel Kurt, Hüll Michael, Fiebich Bernd L
Cerebricon Ltd, Microkatu 1, Kuopio, Finland.
Brain Res. 2005 Aug 9;1052(2):174-9. doi: 10.1016/j.brainres.2005.06.004.
Statins exert beneficial effects in brain diseases including stroke. Here, we investigated whether oral prophylactic atorvastatin provides long-term neuroprotection and functional recovery in permanent middle cerebral artery occlusion (pMCAO), and whether cerebral hemodynamics are affected. Male Long-Evans rats were treated with 10 mg/kg oral atorvastatin for 14 days and subjected to pMCAO. Cerebral hemodynamics were measured by bolus tracking MRI and laser Doppler flowmetry (LDF). Infarct volume was quantified at 1 week by T2-MRI and at 3 weeks by histology. Rats were also subjected to neuroscoring and cylinder test. The number of animals per group was 10. The infarct volumes were 100.8 +/- 8.2 and 47.3 +/- 5.5 mm(3) in vehicle, and 68.7 +/- 11.0 and 28.6 +/- 3.82 mm(3) in atorvastatin group at 7 and 21 days post-ischemia, respectively (mean +/- SEM). Atorvastatin significantly reduced infarct volume both at 7 and 21 days (P = 0.04 and 0.03, respectively, 1-way ANOVA). Interestingly, no improvement in cerebral hemodynamic parameters was observed in atorvastatin treated animals. The vehicle group recovered normal neuroscore at day 13, whereas atorvastatin group recovered already at day 10 after pMCAO. All treatment groups preferred to use the unaffected forelimb for rearing in Cylinder test, whereas the defected forelimb use was minimal in all groups. These results suggest that oral atorvastatin protects cerebral tissue against the subsequent pMCAO without influencing cerebral hemodynamic parameters, and it may well be that persons with ongoing atorvastatin treatment benefit in the incidence of stroke.
他汀类药物对包括中风在内的脑部疾病具有有益作用。在此，我们研究了口服预防性阿托伐他汀是否能在永久性大脑中动脉闭塞（pMCAO）模型中提供长期神经保护和功能恢复，以及是否会影响脑血流动力学。将雄性Long-Evans大鼠用10 mg/kg口服阿托伐他汀治疗14天，然后进行pMCAO手术。通过团注追踪MRI和激光多普勒血流仪（LDF）测量脑血流动力学。在术后1周通过T2-MRI定量梗死体积，在3周时通过组织学方法定量。对大鼠还进行了神经评分和圆筒试验。每组动物数量为10只。在缺血后7天和21天，对照组的梗死体积分别为100.8±8.2和47.3±5.5 mm³，阿托伐他汀组分别为68.7±11.0和28.6±3.82 mm³（均值±标准误）。阿托伐他汀在7天和21天时均显著降低了梗死体积（分别为P = 0.04和0.03，单因素方差分析）。有趣的是，在接受阿托伐他汀治疗的动物中未观察到脑血流动力学参数的改善。对照组在第13天恢复正常神经评分，而阿托伐他汀组在pMCAO术后第10天就已恢复。在圆筒试验中，所有治疗组在站立时都更倾向于使用未受影响的前肢，而所有组中受影响前肢的使用最少。这些结果表明，口服阿托伐他汀可保护脑组织免受随后的pMCAO损伤，而不影响脑血流动力学参数，并且正在接受阿托伐他汀治疗的人可能在中风发病率方面受益。
