O3298: Effect of Parity on Corticosterone and Prolactin 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. One of the most common forms of TBI during operational deployments after Sep 11, 2001 is the blast TBI, responsible for over 80% of TBI sustained in theater. One consequence of TBI is dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. HPA axis dysregulation is linked to increased risk for psychiatric disorders. Prior research has shown that TBI may dysregulate the HPA axis in a sex-dependent manner.
Prolactin increases during pregnancy, returning to pre-pregnancy levels soon after weaning, though it also rises acutely in response to stress. Throughout a female’s life span, there are several sentinel events of hormonal consequence, including pubarche, menopause, and parity, which are known to be times of changes in risks for psychiatric disorders.
The role of parity on TBI response has not been studied, though parity has been shown to decrease fear-related behaviors and decreased corticosterone load in multiparous mice when compared to nulliparous (NP) controls. Hyperprolactinemia is a known consequence of pituitary dysregulation after TBI, but the influence of parity is not known. Our objective is to determine if parity alters corticosterone (CORT) or prolactin (PRL) response to restraint, a mild psychological stressor, in mice exposed to mild blast TBI (mbTBI).

Methods: One hundred thirteen NP or primiparous (PP) C57Bl6/J mice were randomly assigned to receive sham or mbTBI. Among those that received mbTBI (19.2 +/- 0.12 psi), 32 were NP and 24 were PP. Among sham mice, 32 were NP and 26 were PP. All received isoflurane anesthesia prior to sham or mbTBI treatment. At 7-8 days after mbTBI, half the mice were subjected to a mild 20-min restraint before being anesthetized by CO2 followed by collection of trunk blood. Serum was harvested and analyzed for CORT and PRL concentrations by ELISA.

Results: All mice that received mbTBI had a longer (p < 0.05) righting time compared to those that did not. There was no main effect of parity in the righting time (p>0.1). PP mice who experienced mbTBI demonstrated a greater (p < 0.05) CORT response to restraint (157.3 +/- 21 pg/mL) when compared to NP mice (95.9 +/- 7.2 pg/mL). CORT response to restraint did not differ (p>0.1) between NP and PP mice who did not experience mbTBI (96.1 +/- 7.6 vs 109.2 +/- 16 pg/mL). Baseline and prolactin response to restraint did not differ between groups (p>0.07).

Conclusion: Our data indicates that mbTBI alters HPA axis reactivity in PP mice compared to NP mice, increasing the CORT response to restraint induced stress. Parity alone did not alter CORT response to restraint stress, baseline CORT levels, or prolactin response to restraint. The results of our finding highlight the importance of parity as a factor in an individual’s lifespan.