Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Abstract Background Xenon is a noble gas with neuroprotective properties that can improve short and long-term outcomes in young adult mice after controlled cortical impact. This follow-up study investigates the effects of xenon on very long-term outcomes and survival. Methods C57BL/6N young adult male mice ( n =72) received single controlled cortical impact or sham surgery and were treated with either xenon (75% Xe:25% O 2 ) or control gas (75% N 2 :25% O 2 ). Outcomes measured were: (i) 24 h lesion volume and neurological outcome score; (ii) contextual fear conditioning at 2 weeks and 20 months; (iii) corpus callosum white matter quantification; (iv) immunohistological assessment of neuroinflammation and neuronal loss; and (v) long-term survival. Results Xenon treatment significantly reduced secondary injury ( P P P P Conclusions Xenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefits in the treatment of brain trauma patients.