Nah Gabriel D, Antonopoulos Mira N, Hohmann Andrea G, Port Nicholas, Crystal Jonathon D
bioRxiv. 2025 May 2:2025.04.28.651041. doi: 10.1101/2025.04.28.651041.
Mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury. Symptoms following mTBI fall into physical, emotional, sleep, and cognitive categories, with memory deficits being a commonly documented sequelae. Whereas many animal models of mTBI exist, relatively few studies have examined the cognitive deficits of mTBI with human-like cognitive tasks. The Wayne State University Closed Head Weight Drop Model recapitulates critical physical elements of sport-related concussions and trauma-based mTBI. However, until now, this model has not previously been evaluated using a human-like memory task. Rats were trained in an odor-based item-in-context task that dissociates episodic and non-episodic memory (Panoz-Brown et al., Current Biology, 2016). The animals then underwent either a weight drop or a sham procedure. After the manipulation, animals were assessed in the item-in-context task. Episodic memory was significantly impaired in the injured rats by over 10% but not in the sham rats. Non-episodic memory was not impaired in either group. Additionally, a time-course immunohistochemical analysis of the hippocampus was performed to examine possible time-dependent changes in ionized calcium-binding adaptor molecule 1 (iba1), a marker of activated microglia/macrophages and glial fibrillary acidic protein (GFAP), a marker of astrocytes. Concussion injury was associated with time-dependent morphological changes in astrocytes and microglia in injured rats compared to sham rats. This study is the first to document episodic memory impairment in an animal model of mTBI.
轻度创伤性脑损伤（mTBI）是最常见的创伤性脑损伤类型。mTBI后的症状分为身体、情绪、睡眠和认知等类别，记忆缺陷是一种常见的记录在案的后遗症。虽然存在许多mTBI的动物模型，但相对较少的研究使用类似人类的认知任务来研究mTBI的认知缺陷。韦恩州立大学闭合性头部重物坠落模型概括了与运动相关的脑震荡和基于创伤的mTBI的关键物理要素。然而，到目前为止，该模型尚未使用类似人类的记忆任务进行评估。大鼠在基于气味的情境中的物品任务中接受训练，该任务可区分情景记忆和非情景记忆（帕诺兹-布朗等人，《当代生物学》，2016年）。然后，这些动物接受了重物坠落或假手术。操作后，在情境中的物品任务中对动物进行评估。受伤大鼠的情景记忆明显受损超过10%，而假手术大鼠则没有。两组的非情景记忆均未受损。此外，还对海马体进行了时间进程免疫组织化学分析，以检查离子钙结合衔接分子1（iba1，一种活化小胶质细胞/巨噬细胞的标志物）和胶质纤维酸性蛋白（GFAP，一种星形胶质细胞的标志物）可能的时间依赖性变化。与假手术大鼠相比，脑震荡损伤与受伤大鼠星形胶质细胞和小胶质细胞的时间依赖性形态变化有关。这项研究首次记录了mTBI动物模型中的情景记忆损伤。
