Experimental Diffuse Brain Injury Resulted in Sex- and Age-Dependent Changes in Corticosterone

Science Center, Bent Corridor

Cortisol is a glucocorticoid secreted by the adrenal cortex involved in the regulation of stress and inflammation. Clinical data suggest plasma cortisol levels following a traumatic brain injury (TBI) have been correlated with injury severity, recovery time, and quality of life. The mechanical forces associated with the primary injury may injure the pituitary or transect the pituitary stalk leading to endocrine dysfunction. Furthermore, secondary injury processes and exacerbate the injury. We have previously shown chronic decreased corticosterone levels following diffuse TBI following restraint stress. Here, we test the hypothesis that corticosterone levels in the plasma are modulated following experimental diffuse brain injury as a function of sex and age. In the current study, adult male and female rats were subjected to diffuse midline fluid percussion injury or sham surgery. Blood was collected at acute and chronic time points (7, 56, and 168 days post injury). Outcome measures included a weekly weight analysis, terminal plasma corticosterone ELISA assay, and post mortem length and organ weights. Results indicated female shams had a chronic decrease in corticosterone as they age, while brain-injured females had a chronic increase, indicating general recovery. Male corticosterone levels were lower in injured rats compared to uninjured shams, indicative of corticosterone dysfunction. There was an overall sex effect with females having a significantly increased corticosterone across all time points compared to males, independent of injury. In conclusion, these preliminary data demonstrate sex differences in corticosterone, as well as possible chronic corticosterone dysfunction post injury. Further studies are warranted to elucidate endocrine dysfunction following midline fluid percussion injury in the rat. Increasing group sizes may lead to a significant injury effect on corticosterone levels. Future work includes measuring sex hormone differences with a focus on possible neuroprotective mechanisms supported by previous literature. In addition, we will investigate to other signs of pituitary dysfunction measured by both plasma and adrenal hormone levels and histological evidence of neurodegeneration.