title: Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits.
abstract: Repeated mild traumatic brain injury (mTBI) can cause sustained cognitive and psychiatric changes, as well as neurodegeneration, but the underlying mechanisms remain unclear. We examined histologic, neurophysiological, and cognitive changes after single or repeated (three injuries) mTBI using the rat lateral fluid percussion (LFP) model. Repeated mTBI caused substantial neuronal cell loss and significantly increased numbers of activated microglia in both ipsilateral and contralateral hippocampus on post-injury day (PID) 28. Long-term potentiation (LTP) could not be induced on PID 28 after repeated mTBI in ex vivo hippocampal slices from either hemisphere. N-Methyl-D-aspartate (NMDA) receptor-mediated responses were significantly attenuated after repeated mTBI, with no significant changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated responses. Long-term potentiation was elicited in slices after single mTBI, with potentiation significantly increased in ipsilateral versus contralateral hippocampus. After repeated mTBI, rats displayed cognitive impairments in the Morris water maze (MWM) and novel object recognition (NOR) tests. Thus, repeated mTBI causes deficits in the hippocampal function and changes in excitatory synaptic neurotransmission, which are associated with chronic neuroinflammation and neurodegeneration.
authors.affiliation: Department of Anesthesiology, Shock, Trauma, and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Heath Sciences Facility 2 (HSF2), Baltimore, Maryland, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Aungst
authors.affiliation: Department of Anesthesiology, Shock, Trauma, and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Heath Sciences Facility 2 (HSF2), Baltimore, Maryland, USA.
authors.forename: Shruti V
authors.initials: SV
authors.lastname: Kabadi
authors.affiliation: Department of Physiology, University of Maryland School of Medicine Heath Sciences Facility 2 (HSF2), Baltimore, Maryland, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Thompson
authors.affiliation: Department of Anesthesiology, Shock, Trauma, and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Heath Sciences Facility 2 (HSF2), Baltimore, Maryland, USA.
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Stoica
authors.affiliation: Department of Anesthesiology, Shock, Trauma, and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Heath Sciences Facility 2 (HSF2), Baltimore, Maryland, USA.
authors.forename: Alan I
authors.initials: AI
authors.lastname: Faden
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
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