Study reveals how stress affects TBI outcomes in a sex-dependent manner

How stress impacts behavioral outcomes of traumatic brain injury (TBI) represents a major gap in knowledge. This oversight is especially felt by those in the military due to the high prevalence of TBI and the abundance of stress that they endure. In a study funded by the US Department of Defense, researchers led by Pamela VandeVord at Virginia Tech discovered that prior stress exposure influences TBI outcomes in a sex-dependent manner. 

In their eNeuro paper, VandeVord and colleagues used an unpredictable stress paradigm on rats prior to causing TBI using a protocol that mimics brain injuries people experience from explosions during combat. The researchers compared anxiety-like behavior and social motivation in this stress and TBI group to two groups who experienced either stress or TBI alone and another group that experienced none of these. Comparisons revealed sex-dependent differences in behavioral outcomes. Both male groups that experienced stress displayed similar anxiety and social behavior.

But compared to the TBI alone group, stress increased anxiety while protecting some aspects of social motivation in the group of males that experienced both TBI and stress. Female rats with prior stress and TBI had mostly opposite effects regarding social motivation, but their anxiety behaviors were similar to the equivalent male group. Females with only TBI were the most motivated among female groups to socialize with new peers, which was not the case with TBI males.

This study really depicts the importance of looking at pre-existing conditions such as stress and sex and how they influence the outcomes of TBI." 

Pamela VandeVord at Virginia Tech

Source:
Journal reference:

Strickler, J., et al. (2025). Exposure to acute psychological trauma prior to blast neurotrauma results in alternative behavioral outcomes. eNeuro. doi.org/10.1523/ENEURO.0026-24.2025.

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