Genetic Modulators of Traumatic Brain Injury in Animal Models and the Impact of Sex-Dependent Effects

Traumatic brain injury (TBI) is a major health problem causing disability and death worldwide. There is no effective treatment, due in part to the complexity of the injury pathology and factors affecting its outcome. The extent of brain injury depends on the type of insult, age, sex, lifestyle, genetic risk factors, socioeconomic status, other co-injuries, and underlying health problems. This review discusses the genes that have been directly tested in TBI models, and whether their effects are known to be sex-dependent. Sex differences can affect the incidence, symptom onset, pathology, and clinical outcomes following injury. Adult males are more susceptible at the acute phase and females show greater injury in the chronic phase. TBI is not restricted to a single sex; despite variations in the degree of symptom onset and severity, it is important to consider both female and male animals in TBI pre-clinical research studies.