University of Copenhagen, Department of Psychology, Unit for Cognitive Neuroscience, Øster Farimagsgade 2A, Copenhagen 1353, Denmark; KU Leuven, Faculty of Psychology & Educational Sciences, Laboratory of Biological Psychology, Tiensestraat 102 box 3714, Leuven B-3000, Belgium.
KU Leuven, Faculty of Psychology & Educational Sciences, Laboratory of Biological Psychology, Tiensestraat 102 box 3714, Leuven B-3000, Belgium.
Behav Brain Res. 2019 Jun 3;365:222-230. doi: 10.1016/j.bbr.2018.02.040. Epub 2018 Feb 27.
Mild traumatic brain injury (mTBI) can lead to diffuse neurophysical damage as well as cognitive and affective alterations. The nature and extent of behavioral changes after mTBI are still poorly understood and how strong an impact force has to be to cause long-term behavioral changes is not yet known. Here, we examined spatial learning acquisition, retention and reversal in a Morris water maze, and assessed search strategies during task performance after a single, mild, closed-skull traumatic impact referred to as "minimal" TBI. Additionally, we investigated changes in conditioned learning in a contextual fear-conditioning paradigm. Results show transient deficits in spatial memory retention, which, although limited, are indicative of deficits in long-term memory reconsolidation. Interestingly, minimal TBI causes animals to relapse to less effective search strategies, affecting performance after a retention pause. Apart from cognitive deficits, results yielded a sub-acute, transient increase in freezing response after fear conditioning, with no increase in baseline behavior, an indication of a stronger affective reaction to aversive stimuli after minimal TBI or greater susceptibility to stress. Furthermore, western blot analysis showed a short-term increase in hippocampal GFAP expression, most likely indicating astrogliosis, which is typically related to injuries of the central nervous system. Our findings provide evidence that even a very mild impact to the skull can have detectable consequences on the molecular, cognitive and affective-like level. However, these effects seemed to be very transient and reversible.
轻度创伤性脑损伤 (mTBI) 可导致弥漫性神经物理损伤以及认知和情感改变。mTBI 后行为变化的性质和程度仍知之甚少,引起长期行为变化所需的冲击力有多大尚不清楚。在这里,我们在 Morris 水迷宫中检查了空间学习的获得、保留和反转,并在单次轻度闭合性颅骨创伤(称为“最小”TBI)后评估了任务执行过程中的搜索策略。此外,我们还研究了在情境性恐惧条件反射范式中条件学习的变化。结果显示,空间记忆保留存在短暂缺陷,尽管有限,但表明长期记忆再巩固存在缺陷。有趣的是,最小 TBI 导致动物恢复到不太有效的搜索策略,从而影响保留暂停后的表现。除了认知缺陷外,结果还显示恐惧条件反射后出现亚急性、短暂的冻结反应增加,而基线行为没有增加,这表明最小 TBI 后对厌恶刺激的反应更强烈或对压力更敏感。此外,Western blot 分析显示海马 GFAP 表达短期增加,很可能表明星形胶质细胞增生,这通常与中枢神经系统损伤有关。我们的研究结果表明,即使是颅骨的非常轻微的冲击也会对分子、认知和情感水平产生可检测的后果。然而,这些影响似乎非常短暂且可逆。