期刊
STROKE
卷 46, 期 1, 页码 237-244出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.114.007445
关键词
blood-brain barrier; brain edema; cerebral ischemia; KCa3,1 protein, mouse; stroke
资金
- NIA NIH HHS [P30 AG010129] Funding Source: Medline
- NIGMS NIH HHS [R01 GM076063] Funding Source: Medline
- NINDS NIH HHS [R56 NS039953, R01 NS039953] Funding Source: Medline
Background and Purpose-KCa3.1, a calcium-activated potassium channel, regulates ion and fluid secretion in the lung and gastrointestinal tract. It is also expressed on vascular endothelium where it participates in blood pressure regulation. However, the expression and physiological role of KCa3.1 in blood-brain barrier (BBB) endothelium has not been investigated. BBB endothelial cells transport Na+ and Cl- from the blood into the brain transcellularly through the cooperation of multiple cotransporters, exchangers, pumps, and channels. In the early stages of cerebral ischemia, when the BBB is intact, edema formation occurs by processes involving increased BBB transcellular Na+ transport. This study evaluated whether KCa3.1 is expressed on and participates in BBB ion transport. Methods-The expression of KCa3.1 on cultured cerebral microvascular endothelial cells, isolated microvessels, and brain sections was evaluated by Western blot and immunohistochemistry. Activity of KCa3.1 on cerebral microvascular endothelial cells was examined by K+ flux assays and patch-clamp. Magnetic resonance spectroscopy and MRI were used to measure brain Na+ uptake and edema formation in rats with focal ischemic stroke after TRAM-34 treatment. Results-KCa3.1 current and channel protein were identified on bovine cerebral microvascular endothelial cells and freshly isolated rat microvessels. In situ KCa3.1 expression on BBB endothelium was confirmed in rat and human brain sections. TRAM-34 treatment significantly reduced Na+ uptake, and cytotoxic edema in the ischemic brain. Conclusions-BBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 seems to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据