Sex-related responses after traumatic brain injury: Considerations for preclinical modeling

Abstract

Traumatic brain injury (TBI) has historically been viewed as a primarily male problem, since men are more likely to experience a TBI because of more frequent participation in activities that increase risk of head injuries. This male bias is also reflected in preclinical research where mostly male animals have been used in basic and translational science. However, with an aging population in which TBI incidence is increasingly sex-independent due to falls, and increasing female participation in high-risk activities, the attention to potential sex differences in TBI responses and outcomes will become more important. These considerations are especially relevant in designing preclinical animal models of TBI that are more predictive of human responses and outcomes. This review characterizes sex differences following TBI with a special emphasis on the contribution of the female sex hormones, progesterone and estrogen, to these differences. This information is potentially important in developing and customizing TBI treatments.

Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome

“…The onset of WM volume changes may be occurring outside of the critical period in female subjects allowing appropriate compensation for early damage . In addition, estrogen and progestogen in females play a critical neuroprotective function in response to stroke, chronic hypoxia and traumatic brain injury in adulthood . Stroke epidemiology indicates that first stroke occur earlier and are more common in men worldwide .…”

Sex hormones modulate pathogenic processes in experimental traumatic brain injury

“…; Späni et al . ). This study examined whether perioperative administration of the sex steroid synthesis inhibitors LET and FIN alter histopathological, neurological, or molecular parameters after experimental TBI using the CCI model.…”

“…; Späni et al . ). Systemic application of 17β‐estradiol (E2), the most prevalent and potent estrogen, is beneficial after TBI both in male and female rats (Soustiel et al .…”

Microglia dynamics in adolescent traumatic brain injury

“…Common neurological disturbances accompanying mTBIs range from acute symptoms including headache, nausea, dizziness, light/noise sensitivity, attention, concentration, and memory, to more long-term symptoms including irritability, sleep disturbances, anxiety, and depression [ 17 – 19 ]. When accounting for all acquired brain injuries, it appears that males experience more mTBIs than females with apparent sexually dimorphic symptomologies [ 20 ]. For example, when comparing male and female concussed soccer players, Covassin and colleagues found that females performed worse in visual memory tasks, had more total concussive symptoms (verbal and visual memory), and higher rates of migraine-induced cognitive fatigue and sleep disturbances up to 8 days post-injury [ 21 ].…”