Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York, USA.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
J Neurotrauma. 2021 Jul 15;38(14):2030-2045. doi: 10.1089/neu.2020.7398. Epub 2021 Jan 25.
Many military veterans who experienced blast-related traumatic brain injuries (TBI) in the conflicts in Iraq and Afghanistan currently have chronic cognitive and mental health problems including post-traumatic stress disorder (PTSD). Besides static symptoms, new symptoms may emerge or existing symptoms may worsen. TBI is also a risk factor for later development of neurodegenerative diseases. In rats exposed to repetitive low-level blast overpressure (BOP), robust and enduring cognitive and PTSD-related behavioral traits develop that are present for at least one year after blast exposure. Here we determined the time-course of the appearance of these traits by testing rats in the immediate post-blast period. Three cohorts of rats examined within the first eight weeks exhibited no behavioral phenotype or, in one cohort, features of anxiety. None showed the altered cued fear responses or impaired novel object recognition characteristic of the fully developed phenotype. Two cohorts retested 36 to 42 weeks after blast exposure exhibited the expanded behavioral phenotype including anxiety as well as altered cued fear learning and impaired novel object recognition. Combined with previous work, the chronic behavioral phenotype has been observed in six cohorts of blast-exposed rats studied at 3-4 months or longer after blast injury, and the three cohorts studied here document the progressive nature of the cognitive/behavioral phenotype. These studies suggest the existence of a latent, delayed emerging and progressive blast-induced cognitive and behavioral phenotype. The delayed onset has implications for the evolution of post-blast neurobehavioral syndromes in military veterans and its modeling in experimental animals.
许多在伊拉克和阿富汗冲突中经历过爆炸相关创伤性脑损伤 (TBI) 的退伍军人目前患有慢性认知和心理健康问题,包括创伤后应激障碍 (PTSD)。除了静态症状外,新的症状可能会出现或现有的症状可能会恶化。TBI 也是以后发展为神经退行性疾病的一个风险因素。在反复遭受低水平爆炸超压 (BOP) 的大鼠中,会出现强大且持久的认知和 PTSD 相关行为特征,这些特征至少在爆炸暴露后一年仍然存在。在这里,我们通过在爆炸后立即测试大鼠来确定这些特征出现的时间过程。在最初的八周内检查的三组大鼠没有表现出行为表型,或者在一组大鼠中表现出焦虑特征。没有任何一组表现出改变的条件恐惧反应或新物体识别受损,这些都是完全发展的表型特征。在爆炸暴露后 36 到 42 周重新测试的两组大鼠表现出扩展的行为表型,包括焦虑以及改变的条件恐惧学习和受损的新物体识别。结合以前的工作,在爆炸损伤后 3-4 个月或更长时间研究的六组爆炸暴露大鼠中观察到慢性行为表型,而这里研究的三组大鼠记录了认知/行为表型的进展性质。这些研究表明存在潜在的、延迟出现和进展的爆炸诱导认知和行为表型。发病时间的延迟对退伍军人爆炸后神经行为综合征的演变及其在实验动物中的建模具有重要意义。