Expression of Aquaporin-4 Augments Cytotoxic Brain Edema after Traumatic Brain Injury during Acute Ethanol Exposure
Expression of Aquaporin-4 Augments Cytotoxic Brain Edema after Traumatic Brain Injury during Acute Ethanol Exposure
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DOI：
10.1016/j.ajpath.2011.09.011
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发表时间：
2012-01-01
影响因子：
6
通讯作者：
Matsumoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Katada, Ryuichi;Nishitani, Yoko;Matsumoto, Hiroshi
我们之前报道过，乙醇消耗通过 TBI 后的氧化应激加速脑水肿，从而影响创伤性脑损伤 (TBI) 后的发病率和死亡率。水通道蛋白-4 (AQP4) 是一种水通道，参与脑水肿的形成。在这项研究中，我们发现 TBI 后急性乙醇注射会增加 AQP4 的表达，导致大鼠严重脑水肿。在 TBI 之前，用乙醇 (3 g/kg) 或 DL-丁硫氨酸-(S, R)-亚磺酰亚胺 (BSO；100 mg/kg)（一种氧化应激源）对大鼠进行预处理。乙酰唑胺（AQP4 抑制剂）在 TBI 后 3 或 12 小时给予乙醇预处理的大鼠。 TBI 后 24 小时，乙醇和 BSO 预处理组的脑水肿均增加。 TBI 后 24 小时乙醇预处理诱导脂质过氧化。 BSO 和乙醇预处理组的转录因子 NE-kappa B 和缺氧诱导因子 1 α 分别在 TBI 后 3 小时和 24 小时被激活。在乙醇预处理组中，TBI 后 24 小时，AQP4 积累，特别是在星形胶质细胞末端足部。乙酰唑胺治疗将乙醇预处理大鼠的存活率提高至 100%，并减少脑水肿和 AQP4。这些发现表明乙醇会诱导 AQP4 上调，导致脑水肿。 AQP4 的积累可能在乙醇消耗下 TBI 后脑水肿的加重中发挥重要作用。 （Am J Pathol 2012 年，180:17-23；DOL.10.1016/j.ajpath.2011.09.011）
We previously reported that ethanol consumption affects morbidity and mortality after traumatic brain injury (TBI) by accelerating brain edema via oxidative stress after TBI. Aquaporin-4 (AQP4), a water channel, is involved in brain edema formation. In this study, we found that acute ethanol administration increased AQP4 expression after TBI, leading to severe brain edema in rats. Rats were pretreated with ethanol (3 g/kg) or DL-buthionine-(S, R)-sulfoximine (BSO; 100 mg/kg), an oxidative stressor, before TBI. Acetazolamide, an AQP4 inhibitor, was administered to ethanol-pretreated rats 3 or 12 hours after TBI. Brain edema was increased 24 hours after TBI in both the ethanol- and BSO-pretreated groups. Ethanol pretreatment induced lipid peroxidation 24 hours after TBI. Transcription factors, NE-kappa B and hypoxia-inducible factor-1 alpha, were activated 3 and 24 hours after TBI in the BSO- and ethanol-pretreated groups, respectively. In the ethanol-pretreated group, AQP4 was accumulated, particularly in astrocyte end feet, 24 hours after TBI. Acetazolamide treatment improved the survival rate to 100% and decreased brain edema and AQP4 in ethanol-pretreated rats. These findings suggest that ethanol induces up-regulation of AQP4, leading to brain edema. The accumulation of AQP4 may play an important role in the augmentation of brain edema after TBI under ethanol consumption. (Am J Pathol 2012, 180:17-23; DOL. 10.1016/j.ajpath.2011.09.011)