The work included in this thesis investigates the neuroprotective efficacy of the inert gas general anaesthetic xenon in two types of experimental brain injury – blunt traumatic brain injury (TBI) and blast TBI.
The controlled cortical impact (CCI) model of blunt TBI was used in C57BL/6N adult male mice. Xenon 75% given early after the trauma for a period of 3 hours prevented the development of clinically relevant gait and memory deficits and improved survival up to 20 months after the injury. In addition short term neuroprotection was found with xenon concentrations of 30% and 50%.
Two novel blast TBI models, an in vitro and an in vivo model, were developed using a shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform.
In the in vitro blast TBI model C57BL/6N mouse organotypic hippocampal slice cultures were treated with 0.5 atm xenon after exposure to a single shock wave. Cell injury and neuroprotection were quantified by measuring propidium iodide fluorescence. Treatment with xenon 0.5 atm starting one hour after a single blast wave exposure of 55 kPa peak overpressure was found to be neuroprotective.
In the in vivo blast TBI model adult Sprague Dawley male rats were treated with 50% xenon starting early after exposure to three consecutive shock waves of 250 kPa peak overpressure, with xenon treatment lasting for a period of 3 hours. Brain injury and neuroprotection were assessed using microglial cell count. Xenon treatment prevented the development of neuroinflammation 5 days after the injury.
Xenon had no impact on clinically relevant physiologic parameters (heart rate and blood pressure) acutely after the CCI or the blast brain experimental trauma.
These results provide the first evidence of xenon long-term neuroprotection in an animal model of blunt TBI and the first evidence of xenon neuroprotection after blast TBI.