Brief oxygen exposure after traumatic brain injury speeds recovery and promotes adaptive chronic endoplasmic reticulum stress responses.

Traumatic brain injury (TBI) is a major public health concern particularly in adolescents who have a higher mortality and incidence of visual pathway injury compared to adult patients. Likewise, we have found disparities between adult and adolescent TBI outcomes in rodents. Most interestingly, adolescents suffer a prolonged apneic period immediately post injury leading to higher mortality; so, we implemented a brief oxygen exposure paradigm to circumvent this increased mortality. Adolescent male mice experienced a closed-head weight-drop TBI then were exposed to 100% O2 until normal breathing returned or recovered in room air. We followed mice for 7- and 30-days and assessed their optokinetic response; retinal ganglion cell loss; axonal degeneration; glial reactivity; and retinal ER stress protein levels. O2 reduced adolescent mortality by 40%, improved post-injury visual acuity, and reduced axonal degeneration and gliosis in optic projection regions. ER stress protein expression was altered in injured mice, and mice given O2 utilized different ER-stress pathways in a time dependent manner. Finally, O2 exposure may be mediating these ER stress responses through regulation of the redox-sensitive ER folding protein ERO1, which has been linked to a reduction in the toxic effects of free radicals in other animal models of ER stress.