Differences in Axonal Structure Likely Contributing to Increased Vulnerability of Women to Concussions
Although males represent a majority of emergency department visits for sports and recreation-related concussion, researchers have recently found that female athletes have a higher rate of concussion and appear to have worse outcomes than their male counterparts participating in the same sport. University of Pennsylvania researchers have recently identified anatomical differences between male and female axons that may explain this increased vulnerability.
The Penn researchers note, “while the underlying causes of concussion symptoms have yet to be fully characterized, traumatic axonal injury (TAI) has emerged as a primary neuropathological signature” which “likely reflects the unique vulnerability of axons to mechanical damage as the brain undergoes high rotational accelerations.”
Rat and human neurons were used to develop micro-patterned axon tracts in vitro (in a culture dish) that were genetically either male or female. Distinct structural differences were found. Computational modeling of TAI showed that these structural differences placed female axons at greater risk of failure during trauma under the same applied loads as the male axons. Dynamic stretch injury to the axons also induced greater pathophysiology in female axons (including more swelling and greater loss of calcium signaling.)
The researchers offer two possible evolutionary foundations for the observed sex differences. One is that although female brains are smaller in total volume, there is a functional need to maintain a similar number of axons in a given tract for both sexes, resulting in structural differences. For example, in the corpus callosum, although the average axon diameter and total tract volume is greater for males, females have a higher total number of axons. An alternative explanation offered is that since primitive times, as males have preferentially engaged in activities with a risk of head trauma, there may have been an evolutionary advantage to maintain a more mechanically resilient axonal substructure.
More research is needed to fully understand sex differences in brain structure and the implication of these differences for treatment following TBI.