Deferoxamine therapy for intracerebral hemorrhage

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

DESCRIPTION (provided by applicant): Spontaneous intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype. If the patient survives the ictus, the resulting hematoma within brain parenchyma triggers a series of events leading to secondary insults and severe neurological deficits. Although the hematoma in humans gradually resolves, the neurological deficits in ICH patients are usually permanent and disabling. Reproducible ICH models in rats and in pigs have been used extensively to study mechanisms of brain injury. We have developed behavioral tests that can detect prolonged neurological deficits and we and others have found that there is delayed brain atrophy in animal models of ICH. Our recent studies demonstrate that iron overload plays an important role in brain injury following ICH. In particular, we found that systemic administration of the iron chelator deferoxamine can reduce ICH-induced brain injury in adult male rats. The purpose of this translational project is to elucidate an optimal dose and therapeutic time window for deferoxamine therapy in rats and pigs after ICH. In a well-characterized rat model of ICH, deferoxamine will be given systemically. Brain edema formation, brain atrophy and neurological deficits will be examined as endpoints. We will determine: 1) an optimal dose in aged male rats;2) a therapeutic time window in aged male rats. We will then test 3) whether or not the optimal dose/concentration in rats is effective in a well- characterized pig model of ICH and 4) whether or not a therapeutic time window can be found in pigs. The translational research team includes three basic scientists and two clinicians. The NINDS program staff have provided helpful advice during the proposal development. The long-term goal of our studies is to establish a novel and much needed therapy for ICH in humans