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大鼠实验性脑出血后给予阿托伐他汀治疗神经功能结局的改善。

Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats.

作者信息

Seyfried Donald, Han Yuxia, Lu Dunyue, Chen Jieli, Bydon Ali, Chopp Michael

机构信息

Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA.

出版信息

J Neurosurg. 2004 Jul;101(1):104-7. doi: 10.3171/jns.2004.101.1.0104.

Abstract

OBJECT

Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, improves neurological functional outcome, reduces cerebral cell loss, and promotes regional cellular plasticity when administered after intracerebral hemorrhage (ICH) in rats.

METHODS

Autologous blood was stereotactically injected into the right striatum in rats, and atorvastatin was administered orally beginning 24 hours after ICH and continued daily for 1 week. At a dose of 2 mg/kg, atorvastatin significantly reduced the severity of neurological deficit from 2 to 4 weeks after ICH. The area of cell loss in the ipsilateral striatum was also significantly reduced in these animals. Consistent with previous study data, higher doses of atorvastatin (8 mg/kg) did not improve functional outcome or reduce the extent of injury. Histochemical stains for markers of synaptogenesis, immature neurons, and neuronal migration revealed increased labeling in the region of hemorrhage in the atorvastatin-treated rats.

CONCLUSIONS

Analysis of the data in this study indicates that atorvastatin improves neurological recovery after experimental ICH and may do so in part by increasing neuronal plasticity.

摘要

目的

阿托伐他汀是一种β-羟基-β-甲基戊二酰辅酶A还原酶抑制剂,在大鼠脑出血(ICH)后给药时可改善神经功能结局、减少脑细胞损失并促进局部细胞可塑性。

方法

将自体血立体定向注射到大鼠右侧纹状体,脑出血后24小时开始口服阿托伐他汀,持续每日给药1周。剂量为2mg/kg时,阿托伐他汀可显著减轻脑出血后2至4周神经功能缺损的严重程度。这些动物同侧纹状体的细胞损失面积也显著减少。与先前的研究数据一致,更高剂量的阿托伐他汀(8mg/kg)并未改善功能结局或减少损伤程度。对突触形成、未成熟神经元和神经元迁移标志物的组织化学染色显示,阿托伐他汀治疗的大鼠出血区域的标记增加。

结论

本研究数据分析表明,阿托伐他汀可改善实验性脑出血后的神经恢复,且可能部分通过增加神经元可塑性来实现。

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