NSF EPSCoR: Examining Mitochondrial Bioenergetics after Single and Repeated Mild Closed Head Injuries

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Traumatic brain injuries (TBIs) are increasingly becoming a major societal and public health concern with over 1.7 million TBIs reported each year. There is a growing appreciation that mild TBIs, accounting for over 80% of TBIs, can cause cognitive and behavioral impairment. Currently, there is no FDA-approved treatment for patients with TBI. Mitochondrial dysfunction has been observed in animal models of moderate to severe injury, though this has yet to be established as a mechanism that occurs after mild TBI. Using a mouse model of closed head injury (CHI), we will examine the time course (6, 24, 48, and 96 hours after CHI) of mitochondrial dysfunction. Mitochondria function of neurons and glia in the hippocampus and entorhinal cortex will be quantified using a Seahorse Biosciences XF24 Flux Analyzer to measure rates of oxygen consumption in different states of activity. Additionally, platelet mitochondrial bioenergetics will be evaluated as a potential novel biomarker for mild TBI. Memory function, measured by the novel object recognition test (NOR), will be examined at 48 hours after a single mild TBI. Utilizing a time point of maximal mitochondrial dysfunction after mild TBI, we propose to examine to effect of repeated CHI. We hypothesize that multiple mild TBIs at specific time points can induce exacerbated mitochondrial and cognitive impairment. Fundamental understanding of cognitive impairment as related to mitochondrial dysfunction is needed to direct therapeutic technologies.
Effective start/end date1/1/173/31/18


  • University of Rhode Island


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