Sex differences in traumatic brain injury: a multi-dimensional exploration in genes, hormones, cells, individuals, and society

Abstract

Traumatic brain injury (TBI) is exceptionally prevalent in society and often imposes a massive burden on patients’ families and poor prognosis. The evidence reviewed here suggests that gender can influence clinical outcomes of TBI in many aspects, ranges from patients’ mortality and short-term outcome to their long-term outcome, as well as the incidence of cognitive impairment. We mainly focused on the causes and mechanisms underlying the differences between male and female after TBI, from both biological and sociological views. As it turns out that multiple factors contribute to the gender differences after TBI, not merely the perspective of gender and sex hormones. Centered on this, we discussed how female steroid hormones exert neuroprotective effects through the anti-inflammatory and antioxidant mechanism, along with the cognitive impairment and the social integration problems it caused. As to the treatment, both instant and long-term treatment of TBI requires adjustments according to gender. A further study with more focus on this topic is therefore suggested to provide better treatment options for these patients.

Epidemiology of Traumatic Brain Injury in Georgia: A Prospective Hospital-Based Study

“…For example, men have higher TBIs than women, which might be related to societal roles and high engagement in risky activities. [15][16][17][18] As with TBI registries in other countries, the majority of patients sustained mild TBI. 8,17 Prior studies have found that many survivors of TBI have cognitive and physical symptoms, further contributing to the large body of evidence that even mild TBI is associated with long-lasting problems of functioning, especially among young children.…”

Current status of traumatic brain injury research in Malaysia: A systematic review

“…Marching forward, TBI research in Malaysia should also cautiously and statistically account the factors that may influence their research hypotheses on TBI. Factors such as age and gender have been reported to significantly affect TBI outcome (Biswas et al, 2017;Ma et al, 2019;Marquez de la Plata et al, 2008;Munivenkatappa et al, 2016). Some studies have suggested that those 50 years and above (Biswas et al, 2017;Marquez de la Plata et al, 2008) and children (Sariaslan et al, 2016) were at higher risk for poorer prognosis post TBI and were more vulnerable to long term impairments, with TBI in children having been related to late development of functional outcomes and neurodegeneration (Sariaslan et al, 2016).…”

“…Some studies have suggested that those 50 years and above (Biswas et al, 2017;Marquez de la Plata et al, 2008) and children (Sariaslan et al, 2016) were at higher risk for poorer prognosis post TBI and were more vulnerable to long term impairments, with TBI in children having been related to late development of functional outcomes and neurodegeneration (Sariaslan et al, 2016). Gender-wise, while males have reported a higher TBI incidences, females have reported a higher fatality rate and poorer TBI prognosis, based on GCS scores, in some studies (Biswas et al, 2017;Kraus et al, 2000;Munivenkatappa et al, 2016;Wright et al, 2014), despite studies suggesting the neuroprotective effects of female hormones against TBI secondary outcomes (Deutsch et al, 2013;Ma et al, 2019). Despite these findings, majority of the Malaysian TBI population studies had not taken age (33 articles) or gender (36 articles) differences into statistical account.…”

Sex, Genes, and Traumatic Brain Injury (TBI): A Call for a Gender Inclusive Approach to the Study of TBI in the Lab

“…Both clinical and lab studies show a clear influence of sex on TBI outcome. However, whether this is mediated by hormones, genes, or both is still under debate (Gupte et al, 2019;Ma et al, 2019;Mikolić et al, 2020). The majority of research focuses on factors of endogenous hormone signaling (release and reception) in natal males (Slewa-Younan et al, 2004;Dubal et al, 2006;Herson et al, 2009;Griesbach et al, 2015;Clevenger et al, 2018;Mollayeva et al, 2018;Späni et al, 2018;Ma et al, 2019).…”