期刊
EXPERIMENTAL NEUROLOGY
卷 237, 期 2, 页码 453-463出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2012.07.017
关键词
Blood-brain barrier; Ischemic stroke; Tight junction proteins; Caveolin-1; Chinese medicine
资金
- Production of New Medicine Program of Ministry of Science and Technology of the People's Republic of China [2008ZX09401]
- Tianjin Tasly Croup, Tianjin, China [20050230]
Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, for which the current clinical therapy remains unsatisfied. Cerebralcare Granule (R) (CG) is a compound Chinese medicine widely used in China for treatment of cerebrovascular diseases. CG has been demonstrated efficacy in attenuating the cerebral microcirculatory disturbance and hippocampal neuron injury following global cerebral ischemia. However, the effects of CG on BBB disruption following cerebral ischemia have not been investigated. In this study, we examined the therapeutic effect of CG on the BBB disruption in a focal cerebral ischemia/reperfusion (I/R) rat model. Male Sprague-Dawley rats (250 to 300 g) were subjected to 1 h middle cerebral artery occlusion (MCAO). CG (0.4 g/kg or 0.8 g/kg) was administrated orally 3 h after reperfusion for the first time and then once daily up to 6 days. The results showed that Evans blue extravasation, brain water content, albumin leakage, infarction volume and neurological deficits increased in MCAO model rats, and were attenuated significantly by CG treatment. T2-weighted MRI and electron microscopy further confirmed the brain edema reduction in CC-treated rats. Treatment with CG improved cerebral blood flow (CBF). Western blot analysis and confocal microscopy showed that the tight junction proteins claudin-5. JAM-1, occludin and zonula occluden-1 between endothelial cells were significantly degradated, but the protein expression of caveolin-1, the principal marker of caveolae in endothelial cells, increased after ischemia, all of which were alleviated by CG treatment. In conclusion, the post-treatment with CG significantly reduced BBB permeability and brain edema, which were correlated with preventing the degradation of the tight junction proteins and inhibiting the expression of caveolin-1 in the endothelial cells. These findings provide a novel approach to the treatment of ischemic stroke. (C) 2012 Elsevier Inc. All rights reserved.
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