Understanding sex differences in concussion: female vulnerability in concussions

By Esmeralda Carcia-Ramirez. This article was initially published in the 6/27/24 edition of our Concussion Update newsletter; please consider subscribing.

A study published in Acta Neuropathologica found that female swine brains are at a "higher risk of concussion and suffer worse outcomes" than male swine brains. Researchers Hailong Song et al. made this finding based on 16 "clinically relevant swine models" aged approximately 6-8 months, who were given experimental concussions to explore the differences between the sexes in terms of axonal injury. It is worth mentioning that the study only focuses on one area of the brain, the white matter, because damage to axonal fibers in the white matter has been increasingly recognized as a key pathological basis of concussion.

The findings revealed significant structural differences based on staining techniques such as immunohistochemical, immunofluorescent, and transmission electron microscopy. Compared to males, females suffered more swollen axons 24 hours after the concussion and a more widespread loss of axonal sodium channels. Sodium channels are important to the brain because they help with axonal signaling; a concussion disrupts the brain's signaling. Also, concussions selectively result in the loss of smaller diameter axons, and females have a higher proportion of smaller axons, which previous research has revealed. These smaller diameter axons are more vulnerable to traumatic brain injuries. This research study highlights the need for various sex-specific approaches in treating and understanding concussions and other traumatic brain injuries. 

In a press release from Penn Today, senior author Douglas Smith says that understanding sex-specific differences in brain structures supports the use of known biomarkers (such as axon protein fragments) to develop ways to measure injury severity, monitor recovery, and develop new treatments. Understanding sex-based structural differences would also offer insight into how other brain conditions can affect the axons, such as Alzheimer's and Parkinson's. These new findings may reveal some insight for future studies into whether females are more vulnerable to neurodegeneration.