PC2181: Parity Does Not Alter Corticosterone Response to Restraint-induced Stress After Mild Blast Traumatic Brain Injury in Mice

Background: Traumatic brain injury (TBI) affects over 15,000 service members annually. The hypothalamus-pituitary-adrenal axis (HPA) is predisposed to TBI-induced dysregulation. The HPA axis plays a major role in regulating the neuroendocrine stress response and modulates associated neurobehavioral outcomes including anxiety, depression, and post-traumatic stress disorder. Some studies indicate that women are more vulnerable to these adverse outcomes post-TBI. In humans, pregnancy is associated with gray matter volume reduction in regions related to social cognition that persists for 6 years after birth. Prior studies indicate that parous mice have lower fear responses to stress than nulliparous mice. It is unknown if pregnancy alters female response to traumatic brain injury. Pregnancy is known to be a state of elevated cortisol levels in humans, and altered corticosterone response to stressors in mice. Our objective is to determine if parity alters corticosterone response to restraint, a mild psychological stressor, in mice exposed to mild blast TBI (mbTBI).

Methods: Fifty-eight adult primiparous or nulliparous mice were randomly assigned to received sham or mbTBI. They were tested for HPA axis reactivity response 7-8 days post injury. After receiving anesthesia, 13 primiparous and 15 nulliparous mice were exposed to a mild blast TBI with average PSI of 19.32. Fourteen parous and 16 nulliparous mice underwent sham treatment, receiving anesthesia but no mbTBI. At 7 to 8 days after mbTBI, half the subjects were restrained for 20 minutes (stressor) before being anesthetized for rapid decapitation, while the other half did not experience restraint. Serum was collected and analyzed for corticosterone concentrations by ELISA (Enzo Life Sciences).

Results: Restraint-induced corticosterone levels (mean 112.7 ng/mL) were higher than non-restraint-induced levels (mean 28.2 ng/mL) but neither differed between sham and mbTBI groups (p>0.10) or between nulliparous and primiparous groups (p>0.10). There was not a main effect of parity in response to mbTBI (p>0.10).

Conclusion: Our data indicates that corticosterone levels are not altered in parous versus nulliparous mice in response to mbTBI or restraint. These findings suggest that HPA axis basal activity and reactivity response to mbTBI and restraint is not affected by parity. Other studies have suggested that parity may be associated with a resilience phenotype. Going forward, we will examine how parity affects the neural circuitry associated with this phenotype using a transcriptomic approach with unbiased bioinformatics analysis. Based on the results of these analyses, we will investigate additional behavioral outcomes after TBI.