Sex Differences in Long-Term Recovery From Traumatic Brain Injury

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Abstract

Traumatic brain injury (TBI) is a widespread neurological condition suffered by millions of individuals worldwide, including over 2.8 million cases of TBI per year in the U.S. alone. Most frequently induced as a consequence of contact sports, vehicular accidents, and military injuries, TBI can induce post-traumatic epilepsy (PTE), a condition characterized by recurrent, unprovoked seizures as a result of sustained trauma to the brain. Despite the ubiquity of PTE, much of its underlying mechanism and pathophysiology remain unclear. Among other pre-injury factors, biological sex, which has been thought adequately as a critical factor, may have significant impacts on patient outcomes. Further, with more women participating in sports and deploying in military operations than in previous decades, there is an increased demand for understanding the molecular and physiological basis for sex-related variations in recovery from TBI and PTE. In this study, we studied TBI in a female mouse cohort in order to explore the sex-dependent discrepancies associated with PTE. TBI was induced in the subjects before implanting deep-hippocampal electrodes, allowing us to monitor brain activity through EEG analysis. Following the procedures, behavioral testing was performed at various timepoints over a 4-month period before the subjects were sacrificed and their brains removed. We then performed brain histology to determine the extent of neurodegeneration exhibited by the animals. These results were then compared to a previously studied male cohort that underwent an identical protocol. The data shows marked sex differences in functional recovery outcomes of TBI in males and females.

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AED, Antiepileptic Drug AP, Allopregnanolone EEG, Electroencephalography EPM, Elevated Plus Maze LOC, Loss of Consciousness PTE, Post-Traumatic Epilepsy PTS, Post-Traumatic Seizures SE, Status Epilepticus TBI, Traumatic Brain Injury

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