S. Ogle1,2,3, C. Hair1,3, B. Tallent1,3, P. D. Adelson1,3, J. Lifshitz1,3, T. C. Thomas1,3, S. B. Johnson2 1University Of Arizona College Of Medicine,Child Health,Phoenix, AZ, USA 2Banner University Medical Center,Surgery,Phoenix, AZ, USA 3Barrow Neurological Institute At Phoenix Children’s Hospital,Translational Neurotrauma Research Program,Phoenix, AZ, USA
Introduction: Investigations of the etiology of psychiatric morbidity (e.g. post-traumatic stress disorder) after traumatic brain injury (TBI) have suggested a role for circuit reorganization in brain regions associated with emotional processing, such as the amygdala. The fundamental mechanism behind this process is still unknown; however post-traumatic hormonal dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) has been postulated to be involved in dendritic hypertrophy in the amygdala. Previously, we demonstrated increased complexity of glutamatergic projection and inter-neurons in the basolateral amygdala after experimental diffuse TBI up to 28 days post-injury (DPI) and a decrease in plasma corticosterone (rodent equivalent of human cortisol; CORT) at 56 DPI. Decreased cortisol levels in patients with psychiatric morbidity after TBI have been postulated to be a response, in part, to glucocorticoid-receptor (GR) hypersensitivity, GR polymorphism, and dysregulation of the HPA axis; supporting a role for GRs in the pathogenesis of psychiatric morbidity in this population. We therefore hypothesized that experimental diffuse TBI would result in increased GR protein levels in the amygdala in response to late-onset low levels of circulating CORT.
Methods: Adult, male Sprague-Dawley rats underwent a single midline fluid percussion or sham injury and biopsies of the amygdala were evaluated at multiple time-points post-injury for protein levels of GR via automated capillary western. A one-way ANOVA with Fischer’s LSD post-hoc analysis was used for statistical analysis.
Results: GR protein levels significantly changed over time in comparison to sham (F(6,24)=19.28, p=<0.0001). Decreased levels of GR were measured at 3 DPI, with rebound increases in GR protein levels at 14 and 56 DPI.
Conclusion: These data indicate that experimental TBI results in a chronic evolving sequaelae of events over at least 2 months post-injury and represent a potential mechanism by which the pathogenesis of psychiatric morbidity develops after TBI.