Lethal apnea is a significant cause of acute mortality following a severe traumatic brain injury (TBI). TBI is associated with a surge of adenosine, which also suppresses respiratory function in the brainstem. This study examined the acute and chronic effects of caffeine, an adenosine receptor antagonist, on acute mortality and morbidity after fluid percussion injury. We demonstrate that, regardless of preinjury caffeine exposure, an acute bolus of caffeine given immediately following the injury dosedependently prevented lethal apnea and has no detrimental effects on motor performance following sublethal injuries. Finally, we demonstrate that chronic caffeine treatment after injury, but not caffeine withdrawal, impairs recovery of motor function. Preexposure of the injured brain to caffeine does not have a major impact on acute and delayed outcome parameters; more importantly, a single acute dose of caffeine after the injury can prevent lethal apnea regardless of chronic caffeine preexposure.Copyright 2020, Mary Ann Liebert, Inc., publishers.
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