Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury.
Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury.
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DOI：
10.1155/2019/2831501
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发表时间：
2019-01-01
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影响因子：
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通讯作者：
Sayre, Naomi L
中科院分区：
文献类型：
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作者：
Glober, Nancy K;Sprague, Shane;Sayre, Naomi L
创伤性脑损伤（TBI）后，多个持续的过程会导致原发损伤的恶化和扩散，从而产生继发性损伤。一个主要的过程涉及破坏液体调节，在受累区域产生血管性和细胞毒性水肿。虽然对影响水肿的因素了解尚不完整，但星形胶质细胞水通道水通道蛋白4 （AQP4）已被确定为重要的介质，因此是预防水肿的有吸引力的药物靶点。fda批准的药物乙酰唑胺在美国已经安全使用多年。为了检测乙酰唑胺是否改变了脑外伤后AQP4的功能，我们采用了体外和体内模型。我们的研究结果表明，脑外伤后AQP4的定位发生了改变，这与之前发表的报道相似。乙酰唑胺在体外和小鼠体内均可阻止AQP4重组。此外，乙酰唑胺在我们的小鼠TBI模型中消除了细胞毒性水肿。我们的结果提示乙酰唑胺在TBI治疗中的可能的临床作用。
After traumatic brain injury (TBI), multiple ongoing processes contribute to worsening and spreading of the primary injury to create a secondary injury. One major process involves disrupted fluid regulation to create vascular and cytotoxic edema in the affected area. Although understanding of factors that influence edema is incomplete, the astrocyte water channel Aquaporin 4 (AQP4) has been identified as an important mediator and therefore attractive drug target for edema prevention. The FDA-approved drug acetazolamide has been administered safely to patients for years in the United States. To test whether acetazolamide altered AQP4 function after TBI, we utilized in vitro and in vivo models of TBI. Our results suggest that AQP4 localization is altered after TBI, similar to previously published reports. Treatment with acetazolamide prevented AQP4 reorganization, both in human astrocyte in vitro and in mice in vivo. Moreover, acetazolamide eliminated cytotoxic edema in our in vivo mouse TBI model. Our results suggest a possible clinical role for acetazolamide in the treatment of TBI.