Differential effects of glucocorticoid and mineralocorticoid antagonism on anxiety behavior in mild traumatic brain injury
Differential effects of glucocorticoid and mineralocorticoid antagonism on anxiety behavior in mild traumatic brain injury
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DOI：
10.1016/j.bbr.2016.06.048
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发表时间：
2016-10-01
影响因子：
2.7
通讯作者：
Forster, Gina L.
中科院分区：
文献类型：
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作者：
Fox, Laura C.;Davies, Daniel R.;Forster, Gina L.
轻度创伤性脑损伤（tbi）占美国每年发生的所有tbi的四分之三，并且由此引起的心理症状可能在受伤后持续数年。轻度脑外伤后常见的症状是广泛性焦虑。大多数轻度脑损伤发生在紧张的情况下（运动、战争、家庭暴力等），当脑中的糖皮质激素在撞击时升高，糖皮质激素对脑损伤后的神经元健康有负面影响。因此，阻断糖皮质激素受体可能会阻止损伤后焦虑症状的出现。成年雄性大鼠在暴露于急性社会失败应激后立即发生轻度脑损伤前40分钟，分别给予米非司酮（20 mg/kg）或螺内酯（50 mg/kg）阻断糖皮质激素和矿皮质激素受体。在伴有轻度TBI的失败大鼠中，米非司酮将在高水平迷宫中张开双臂的时间恢复到控制水平，首次证明糖皮质激素受体在轻度TBI后焦虑的发展中起关键作用。未来的治疗可以针对这些受体，减轻焦虑，这是在压力情况下持续的轻度TBI受害者的主要副作用。(C) 2016 Elsevier B.V.版权所有
Mild traumatic brain injuries (TBIs) comprise three-quarters of all TBIs occurring in the United States annually, and psychological symptoms arising from them can last years after injury. One commonly observed symptom following mild TBI is generalized anxiety. Most mild TBIs happen in stressful situations (sports, war, domestic violence, etc.) when glucocorticoids are elevated in the brain at the time of impact, and glucocorticoids have negative effects on neuronal health following TBI. Therefore, blocking glucocorticoid receptors might prevent emergence of anxiety symptoms post-injury. Adult male rats received mifepristone (20 mg/kg) or spironolactone (50 mg/kg) to block glucocorticoid and mineralocorticoid receptors, respectively, 40 min prior to being exposed to acute social defeat stress followed immediately by mild TBI. In defeated rats with concomitant mild TBI, mifepristone restored time spent in the open arms of an elevated plus maze to control levels, demonstrating for the first time that glucocorticoid receptors play a critical role in the development of anxiety after mild TBI. Future treatments could target these receptors, alleviating anxiety as a major side effect in victims of mild TBI sustained in stressful situations. (C) 2016 Elsevier B.V. All rights reserved.