Researchers in the College of Medicine who have studied traumatic brain injuries for decades are revealing new insights about how and why the brains of male and female concussion patients recover differently.

Using swim and maze tests, Professor Ramesh Raghupathi and colleagues found that female rats with past adolescent traumatic brain injury were more likely to develop depression-like behavior in adulthood than their male counterparts. They also found that this behavior — recorded six weeks after the injury — took place during the estrus phase of the reproductive cycle, which occurs after estrogen and progesterone hormone levels drop in the body, suggesting a depression-like characteristic.

When young male and female rats experience traumatic brain injury (shown in brain slices B,D), female rats were more likely to succumb to subsequent depression. It is theorized that regulating hormones during the proestrus phase may be a more targeted treatment than long-term anti-depressants.

The team took this knowledge a step further, blocking estrogen and progesterone receptors with the drugs tamoxifen and mifepristone during the proestrus phase, when these hormones would otherwise be at their highest levels. This intervention prevented depression-like behaviors that previously occur only in specific phases of the reproductive cycle — right after the increase in estrogen and progesterone.

“Hormones play a critical role in regulating depression after a traumatic brain injury,” says Raghupathi, who reported his findings in the Journal of Neuroscience Research in 2022. “Therapies that target these hormones may help alleviate or even prevent depression for millions of women and girls suffering from a history of these brain injuries.”

The researchers determined that the behavioral changes were triggered by a combination of injury and hormones in the estrous period — not the injury or reproductive cycle alone.