Repetitive closed-head impact model of engineered rotational acceleration (CHIMERA) injury in rats increases impulsivity, decreases dopaminergic innervation in the olfactory tubercle and generates white matter inflammation, tau phosphorylation and degeneration
Repetitive closed-head impact model of engineered rotational acceleration (CHIMERA) injury in rats increases impulsivity, decreases dopaminergic innervation in the olfactory tubercle and generates white matter inflammation, tau phosphorylation and degeneration
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DOI：
10.1016/j.expneurol.2019.02.012
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发表时间：
2019-07-01
影响因子：
5.3
通讯作者：
Wellington, Cheryl L.
中科院分区：
文献类型：
--
作者：
Haar, Cole Vonder;Martens, Kris M.;Wellington, Cheryl L.
创伤性脑损伤每年至少影响300万人。在人类中，重复性轻度脑损伤(RmTBI)可导致冲动增加，并可能与慢性创伤性脑病有关。为了更好地了解重复脑损伤(RTBI)、冲动性和神经病理学之间的关系，我们使用工程旋转加速的闭合头部损伤模型(Chimera)给大鼠提供了五次脑损伤，并使用延迟折扣任务连续评估了大鼠的特质冲动性和终点的神经病理学。与假手术对照组相比，RTBI组大鼠在冲动选择中表现出进行性损害。组织学分析显示，从腹侧被盖区到嗅结节的多巴胺能神经支配减少，与冲动神经回路的改变一致。与嵌合体所致弥漫性轴索损伤相一致，在视束和穹隆体内可见白质炎症、tau免疫反应和变性。最后，嗅结节内可见明显的灰质小胶质细胞增多症。我们的结果为RTBI在一个新的大鼠脑外伤平台上导致创伤后精神病样症状的机制提供了洞察力。
Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint. Compared to sham controls, rats with rTBI displayed progressive impairment in impulsive choice. Histological analyses revealed reduced dopaminergic innervation from the ventral tegmental area to the olfactory tubercle, consistent with altered impulsivity neurocircuitry. Consistent with diffuse axonal injury generated by CHIMERA, white matter inflammation, tau immunoreactivity and degeneration were observed in the optic tract and corpus callosum. Finally, pronounced grey matter microgliosis was observed in the olfactory tubercle. Our results provide insight into the mechanisms by which rTBI leads to post-traumatic psychiatric-like symptoms in a novel rat TBI platform.