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Sex Differences in Experimental Traumatic Brain Injury‐induced Epileptogenesis
Author(s) -
Golub Victoria,
Calderara Gianni,
Reddy Samba
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03108
Subject(s) - traumatic brain injury , epileptogenesis , medicine , astrogliosis , gliosis , physiology , psychology , hippocampus , pathology , central nervous system , psychiatry
Traumatic brain injury (TBI) is a complex condition that affects millions of people worldwide. TBI has both immediate and long‐term pathological consequences, and individual cases are graded as minor, moderate, or severe based on the Glasgow Coma Scale. Among the numerous factors that influence prognosis, gender is perhaps the most notable because of hormonal factors. It has been shown that progesterone, a female steroid hormone with reproductive and neuroactive effects, has improved motor function and mortality rates in patients post‐severe TBI. In this study, we sought to investigate the sex differences in progression of spontaneous recurrent seizures and long‐term inflammation after TBI. We used a controlled cortical‐hippocampal impact (CCI) model of severe TBI in adult male and cycling female mice. They were monitored by 24/7 by video‐EEG recording g for 4 months through a recording electrode placed in the contralateral hippocampus. Behavioral and motor analyses were assessed over a 4‐month period and tests consisted of beam‐walk, neuroscore, rotarod, elevated plus maze, and novel object recognition. Brains were post‐fixed for immunohistochemistry and analyzed for astrogliosis (GFAP+) and microgliosis (IBA1+). Epileptic seizures were identified in both the male and female mice, though incidence and frequency were significantly lower in the female cohort with CCI. Reactive gliosis and astrocyte activated persisted through 4 months post‐TBI, indicating a chronic inflammatory response. Additionally, female mice displayed significantly improved functional and sensory‐motor performance compared to age‐matched males. Hormones impacts many aspects of TBI including clinical manifestations, recovery outcomes, and quality of life. Our results characterize striking sex differences in TBI‐induced epileptogenesis and its associated comorbidities which has implications to develop sex‐specific treatments and improve prognosis.