Researchers identified differences in axon structure between males and females that may help explain why concussion often led to more severe symptoms and prolonged recovery in women and girls, according to a study.

Using a clinically relevant swine model, study investigators found that 24 hours after experiencing a concussion-like injury, female swine displayed a 58% greater number of swollen and degenerating axons in critical white matter tracts compared to males subjected to the same forces.

The researchers suggested that this underlying structural difference may have made female axons more vulnerable to the biomechanical forces of concussion. Diffuse axonal injury, where axons across the white matter showed transport interruption, swelling and degeneration, was considered one of the key pathological features of concussion.

In addition to greater axonal swelling, the team observed a 23% more extensive loss of sodium channels along axons in female swine after the injury. The loss of axonal sodium channels reflected a loss of ionic homeostasis that could disrupt the central component of axonal signaling machinery, the generation of action potentials. This may have represented a potential physiologic disruption of functional connectivity and potentially accounted for the longer recovery duration in females, which averaged 50% longer than males in the study.

The study, published in Acta Neuropathologica, also found that female axons were, on average, 32% smaller in diameter compared to male axons, which the researchers proposed may have contributed to their greater vulnerability to injury.

The study helped provide a pathological basis for the growing clinical evidence that women and girls suffered higher rates of concussion and often faced worse outcomes than their male counterparts in the same sports. However, the authors noted that more research was needed to establish a more comprehensive spatial distribution of axonal pathologies and to examine the decrease in sodium channels in relevance to functional outcomes.

The findings from this study could potentially support future research into developing blood biomarkers and advanced neuroimaging approaches to better detect and monitor sex differences in axonal damage after concussion. 

Authors declared that they had no competing interests.