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

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posted on 15.03.2021, 21:16 authored by Louise PhamLouise Pham, DK Wright, WT O'Brien, J Bain, C Huang, M Sun, PM Casillas-Espinosa, AD Shah, RB Schittenhelm, Christopher SobeyChristopher Sobey, RD Brady, TJ O'Brien, R Mychasiuk, SR Shultz, Stuart McDonaldStuart McDonald
© 2020 The Author(s) 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.


PMC, TJO, RM and SRS would like to thank the Australian National Health and Medical Research Council for funding. This work was supported by an Australian Government Research Training Program Scholarship. The authors would also like to thank Mrs. Karen Griggs for her assistance throughout this project.


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Neurobiology of Disease



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