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爆炸导致的“创伤后应激障碍”:来自动物模型的证据。

Blast-induced "PTSD": Evidence from an animal model.

机构信息

Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA.

General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY 10468, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA.

出版信息

Neuropharmacology. 2019 Feb;145(Pt B):220-229. doi: 10.1016/j.neuropharm.2018.09.023. Epub 2018 Sep 15.

Abstract

A striking observation among veterans returning from the recent conflicts in Iraq and Afghanistan has been the co-occurrence of blast-related mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might coexist due to additive effects of independent psychological and physical traumas experienced in a war zone. Alternatively blast injury might induce PTSD-related traits or damage brain structures that mediate responses to psychological stressors, increasing the likelihood that PTSD will develop following a subsequent psychological stressor. Rats exposed to repetitive low-level blasts consisting of three 74.5 kPa exposures delivered once daily for three consecutive days develop a variety of anxiety and PTSD-related behavioral traits that are present for at least 9 months after blast exposure. A single predator scent challenge delivered 8 months after the last blast exposure induces additional anxiety-related changes that are still present 45 days later. Because the blast injuries occur under general anesthesia, it appears that blast exposure in the absence of a psychological stressor can induce chronic PTSD-related traits. The reaction to a predator scent challenge delivered many months after blast exposure suggests that blast exposure in addition sensitizes the brain to react abnormally to subsequent psychological stressors. The development of PTSD-related behavioral traits in the absence of a psychological stressor suggests the existence of blast-induced "PTSD". Findings that PTSD-related behavioral traits can be reversed by BCI-838, a group II metabotropic glutamate receptor antagonist offers insight into pathogenesis and possible treatment options for blast-related brain injury. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".

摘要

在最近从伊拉克和阿富汗冲突中返回的退伍军人中,一个引人注目的观察结果是爆炸相关的轻度创伤性脑损伤(mTBI)和创伤后应激障碍(PTSD)同时发生。PTSD 和 mTBI 可能同时存在,因为战区经历的独立心理和身体创伤的附加效应。或者,爆炸伤可能会引起与 PTSD 相关的特征,或损害介导对心理应激源反应的大脑结构,增加 PTSD 在随后的心理应激源后发展的可能性。暴露于重复的低水平爆炸中的大鼠,包括每天连续三天暴露三次 74.5kPa 的爆炸,会发展出各种焦虑和与 PTSD 相关的行为特征,这些特征在爆炸暴露后至少 9 个月仍然存在。在最后一次爆炸暴露 8 个月后进行的单次捕食者气味挑战会引起额外的与焦虑相关的变化,这些变化在 45 天后仍然存在。由于爆炸伤是在全身麻醉下发生的,因此似乎在没有心理应激源的情况下暴露于爆炸中会引起慢性与 PTSD 相关的特征。在爆炸暴露后数月进行的捕食者气味挑战的反应表明,爆炸暴露除了使大脑对随后的心理应激源异常敏感之外。在没有心理应激源的情况下发生的与 PTSD 相关的行为特征表明存在与爆炸相关的“PTSD”。发现与 PTSD 相关的行为特征可以通过 BCI-838 逆转,BCI-838 是一种 II 型代谢型谷氨酸受体拮抗剂,为爆炸相关脑损伤的发病机制和可能的治疗选择提供了深入了解。本文是题为“创伤性脑损伤的新治疗方法”的特刊的一部分。

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