Secondary Brain Injury in Intracerebral Hemorrhage

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DESCRIPTION (provided by applicant): Acute primary non-traumatic intracerebral hemorrhage (ICH) is a common disorder for which there is currently no therapy of proven benefit in improving mortality and functional outcome. In fact, there remains controversy regarding the mechanisms by which ICH creates primary and secondary brain injury. The overall objective of this proposal is to produce a program which combines didactic teaching, mentoring, and clinical research to build upon Dr. Hemphill's training in neurologic critical care, thereby allowing him to develop into an independent clinical investigator studying mechanisms of injury and treatment of ICH. While management decisions in ischemic stroke, head trauma, and subarachnoid hemorrhage may be made based on clinical and diagnostic monitoring for secondary brain injury, the usefulness of this in ICH is not known. The overall hypothesis for this project is that secondary brain injury adversely effects outcome after ICH and that approaches that decrease secondary brain injury after ICH will improve outcome. This will be investigated through a series of studies related to clinical, neuromonitoring, and neuroimaging evaluation of secondary brain injury in ICH, culminating in a pilot clinical trial of ICH treatment. Studies will address: 1) the impact of clinical secondary brain insults (systemic hypoxia, hypotension, fever, and seizures) on outcome, 2) the influence of brain tissue hypoxia (measured through direct monitoring of brain tissue oxygen tension in the neurologic intensive care unit) on outcome, 3) the correlation between brain tissue hypoxia and ischemia on dynamic CT perfusion and MR diffusion-weighted imaging, and 4) the feasibility of targeting secondary brain injury in a pilot study of ICH treatment. This research should provide new and important information about the role of secondary brain injury in ICH. In conjunction with the didactic training and mentoring undertaken, this program will foster Dr. Hemphill's development into an independent researcher in neurologic critical care, specifically focusing on intracerebral hemorrhage.