Introduction Traumatic brain injury (TBI) affects both young and elderly populations and results in a significant global healthcare burden. TBI patients often suffer from costly long-term neurological and cognitive problems that reduce quality of life and ability to work, including motor deficits, gait abnormalities, memory impairments and anxiety. Current clinical practice for TBI is largely supportive, centred on non-specific endpoints such as management of tissue oxygenation, cerebral perfusion pressure and intracranial pressure. At present there are no clinically validated drug treatments aimed specifically at preventing neuronal loss following TBI. Xenon is a noble gas used medically as a general anaesthetic and in MRI imaging. We previously showed xenon-treatment improves short and long-term outcomes, prevents late-onset cognitive impairments and improves survival after moderate TBI in mice. The aim of this study is to evaluate the efficacy of xenon in a second species, rats, and in a severe injury model.

Method Adult male Sprague Dawley rats (N=22) underwent controlled cortical impact (CCI) brain trauma or sham surgery. Animals were randomised to receive either 50%Xe:25%O2:25%N2 or 75%N2:25%O2. Locomotor function (CatwalkXT) and histological outcomes [lesion volume, neuronal cell count (NeuN), microglia (Iba1) and astrocytes (GFAP)] were assessed by blinded observers.

Results The xenon-treated group exhibited a reduction in locomotor deficits. Lesion volume was reduced in the xenon-treated group. Xenon-treatment resulted in preservation of neurons in cortical and subcortical regions that was associated with increases in numbers of resting microglia and reactive astrocytes.

Conclusion We show xenon is neuroprotective after severe TBI in rats. Functional improvement and neuronal preservation was associated with a xenon-induced enhancement of resting microglial cell numbers and astrocyte activation. These findings are consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. Xenon may be of benefit in the treatment of clinical brain trauma.