Behavioral, axonal, and proteomic alterations following repeated mild traumatic brain injury: Novel insights using a clinically relevant rat model

创伤性脑损伤 神经病理学 神经炎症 神经科学 脑震荡 白质 心理学 海马结构 医学 弥漫性轴索损伤 磁共振弥散成像 海马体 磁共振成像 毒物控制 内科学 精神科 伤害预防 炎症 放射科 疾病 环境卫生
作者
Louise Pham,David Wright,William T. O’Brien,Jesse Bain,Cheng Huang,Mujun Sun,Pablo M. Casillas‐Espinosa,Anup D. Shah,Ralf B. Schittenhelm,Christopher G. Sobey,Rhys D. Brady,Terence J. O’Brien,Richelle Mychasiuk,Sandy R. Shultz,Stuart J. McDonald
出处
期刊:Neurobiology of Disease [Elsevier BV]
卷期号:148: 105151-105151 被引量:31
标识
DOI:10.1016/j.nbd.2020.105151
摘要

A history of mild traumatic brain injury (mTBI) is linked to a number of chronic neurological conditions, however there is still much unknown about the underlying mechanisms. To provide new insights, this study used a clinically relevant model of repeated mTBI in rats to characterize the acute and chronic neuropathological and neurobehavioral consequences of these injuries. Rats were given four sham-injuries or four mTBIs and allocated to 7-day or 3.5-months post-injury recovery groups. Behavioral analysis assessed sensorimotor function, locomotion, anxiety, and spatial memory. Neuropathological analysis included serum quantification of neurofilament light (NfL), mass spectrometry of the hippocampal proteome, and ex vivo magnetic resonance imaging (MRI). Repeated mTBI rats had evidence of acute cognitive deficits and prolonged sensorimotor impairments. Serum NfL was elevated at 7 days post injury, with levels correlating with sensorimotor deficits; however, no NfL differences were observed at 3.5 months. Several hippocampal proteins were altered by repeated mTBI, including those associated with energy metabolism, neuroinflammation, and impaired neurogenic capacity. Diffusion MRI analysis at 3.5 months found widespread reductions in white matter integrity. Taken together, these findings provide novel insights into the nature and progression of repeated mTBI neuropathology that may underlie lingering or chronic neurobehavioral deficits.
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