Age-dependent differences in glutathione peroxidase activity after traumatic brain injury

Children younger than 4 years old have worse outcome after traumatic brain injury (TBI) compared to older children and adults. This increased susceptibility may in part be due to differences in the response to oxidative stress. We hypothesized that the immature brain does not have an adequate compensatory response to injury from oxidative stress. To begin to address this hypothesis, we first compared the general dimensions and water content in postnatal day 21 (P21) and adult murine brain in the naive state as well as after injury (edema). We examined glutathione peroxidase (GPx) activity in cortical and subcortical regions in P21 and adult murine brain following a controlled cortical impact. Brain dimensions including areas of the mantle and hemispheres were similar in each of these groups. The thickness of the cortical mantle was significantly greater in the immature brain as compared to the mature brain (p = 0.01, respectively). Brain edema was assessed through changes in water content, and the response to oxidative challenge was identified by changes in GPx activity. The P21 brain was similar in vulnerability to posttraumatic brain edema when compared to adult. GPx activity in the adult brain was increased within 24 h post-injury in the cortex, thalamus and hippocampus (ANOVA, p < 0.05), whereas there was no compensatory increase in GPx activity in P21 brain, although baseline levels had reached adult levels developmentally. These findings support our hypothesis and illuminate the important role of oxidative stress after TBI in the immature brain that warrants further study.