Experimental Intracerebral Hemorrhage

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Intracerebral hemorrhage (ICH) causes approximately 10 percent of strokes. It is particularly important because younger stroke victims are commonly affected, and ICH hemorrhaging is the most feared complication of acute thrombolytic therapy, the only generally accepted treatment for ischemic stroke. We currently have no proven therapy for most types of ICH. Although tissue plasminogen therapy for stroke was FDA approved in 1996, at the present time, only about 2 percent of stroke victims in the United States receive this highly effective treatment. Thus, investigations of methods for reducing the damage caused by ICH should provide a basis for treating patients with primary ICH and protecting the much larger group of ischemic stroke victims. We propose to investigate both fundamental structural and biochemical abnormalities that cause ICH, and to develop pharmacological methods for reducing the extent of hemorrhaging and its secondary neurological consequences. We have already shown that several drugs that influence cerebral inflammatory responses to ICH can reduce both hemorrhaging and neurological damage in our ICH models. We also have preliminary data showing that histopathological and biochemical methods are valuable for investigating some of the causes of hemorrhaging. For these studies, we propose to employ a coordinated set of animal models that facilitate pharmacological and more basic studies. We propose to further define the types of neuroprotective drugs that reduce ICH induced neurological damage caused inflammatory reactions. We also plan to investigate the interactions between blood pressure, thrombolytic agents and ICH. This may provide insights as to how best to manage acute stroke victims. Finally, we intend to investigate the biochemical relationships between ICH and purely ischemic strokes using biochemical tools. These studies may provide insights about the causes of bleeding and neurological tissue damage that should be helpful in designing even more effective stroke therapies.