David S. Warner, MD, Director of the Multidisciplinary Neuroprotection Laboratories received a 2-year $793,750 NIH Exploratory/Development Research Grant (R21) from the National Institute of Neurological Disorders and Stroke entitled “Xenon as a Therapeutic Experimental Intracerebral Hemorrhage”.
Intracerebral hemorrhage (ICH) is a form of stroke. There is little treatment option other than supportive care. Xenon (Xe) is an inert gas which has undergone intensive preclinical investigation in models of brain injury and is currently being investigated as an adjunct to hypothermia for treatment of anoxic/asphyxia brain injury in humans. It has few side effects and is available for human use. We found Xe improves neurologic outcome from experimental ICH and offers major advantages to the injured brain. It has rapid BBB penetration, modulates the NMDA glycine recognition site without psychotomimetic effects, and has negligible effects on intracranial pressure and cardiovascular function. We recently investigated Xe in a rodent transient focal ischemic stroke model. While post-ischemic Xe improved short-term outcome, long-term outcome was improved only when Xe was combined with reduction of brain temperature to 36°C. This offered sufficient clinical relevance to lead us to explore the effect of Xe in two different mouse ICH models. While the goal was to rule out a potential adverse effect of Xe in ICH should Xe be applied clinically prior to imaging for ischemic stroke, we were surprised that to the contrary, Xe repeatedly improved both histologic and functional ICH outcome and decreased brain water content and microglial activation. The goal of the project is to subject Xe to a sequence of rigorous preclinical studies specifically designed to advance Xe to human ICH trials.