Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy
Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy
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DOI：
10.1002/glia.20174
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发表时间：
2005-06-01
期刊：
影响因子：
6.2
通讯作者：
Kimelberg, HK
中科院分区：
文献类型：
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作者：
Kimelberg, HK
在这篇观点文章中，我总结了在急性中枢神经系统病理、缺血和创伤性脑损伤后早期发生的星形细胞肿胀是破坏性的。我们提出其中一个原因可能是兴奋性氨基酸（EAA）通过体积活化阴离子通道（vrac）释放，该通道被这种肿胀激活。这种释放可能是治疗的目标，可能包括阻断星形细胞肿胀或释放机制。因此总结了可能引起早期星形细胞肿胀的转运机制。在靶向释放机制方面，我们发现一种有效的vrac抑制剂他莫昔芬在局灶性缺血中具有很强的神经保护作用，其治疗窗口期为缺血开始后3小时。然而，他莫昔芬的神经保护作用是否完全归因于星形胶质细胞中VRAC的抑制，这一问题尚未得到解决。(c) 2005 Wiley-Liss, Inc。
In this viewpoint article, I summarize data showing that the astrocytic swelling that occurs early after the acute CNS pathologies ischemia and traumatic brain injury is damaging. We have proposed that one reason may be the release of excitatory amino acids (EAA) via volume-activated anion channels (VRACs) that are activated by such swelling. This release could be a target for therapy, which could involve blocking the astrocytic swelling or the release mechanisms. The transport mechanisms likely causing the early astrocytic swelling are therefore summarized. In terms of targeting the release mechanisms, we have found a potent inhibitor of VRACs, tamoxifen, to be strongly neuroprotective in focal ischemia with a therapeutic window of 3 h after initiation of the ischemia. The question, however, of whether neuroprotection by tamoxifen can be solely attributed to VRAC inhibition in astrocytes has yet to be resolved. (c) 2005 Wiley-Liss, Inc.