Therapeutic targeting of CD36 after intracerebral hemorrhage

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DESCRIPTION (provided by applicant): Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, accounts for up to 15% of all strokes, with 37,000-52,400 Americans suffering an ICH annually. ICH has the highest acute mortality and the worst long-term neurological outcomes of all types of stroke. ICH is caused by a ruptured blood vessel within the brain, leading to the formation of a space occupying hematoma. Hematoma volume is clinically associated with neurological deterioration and higher mortality; however, many ICH patients are poor surgical candidates and/or present with an unfavorable size/location of the lesion, restricting the utility of neurosurgical intervention. Furthermore, efficacious medical treatment options to promote hematoma clearance are lacking, presenting a critical barrier to clinical practice. Our long-term objective is to identify the molecular and cellular pathways which contribute to clot resolution after ICH. This knowledge will provide a framework for pharmaceutical development to improve patient outcomes after ICH. Our pilot data suggest the curry spice, curcumin, promotes hematoma resolution after ICH and may therefore represent a novel and safe treatment option. Specific Aim 1 will test the hypothesis that CD36 mediates curcumin-induced hematoma clearance after ICH. Specific Aim 2 will test the hypothesis that C/EBP-¿ mediates curcumin-induced CD36 expression and hematoma resolution after ICH. Together, the proposed studies will elucidate the molecular and cellular mechanisms which underlie the ability of curcumin to promote hematoma resolution. The results of these studies will provide a framework for pharmaceutical development targeting C/EBP-¿ and/or CD36 to improve clinical outcomes after ICH. PUBLIC HEALTH RELEVANCE: Intracerebral hemorrhage (ICH), the most common type of hemorrhage stroke, is induced by a ruptured blood vessel, resulting in the formation of a space-occupying hematoma (blood clot) within the brain. Hematoma volume is associated with increased patient mortality; however, few treatment options are available to eliminate the clot. Given that the rate of ICH incidence is expected to double over the next 50 years as a result of an aging population and increased risk factors (e.g. hypertension, diabetes), novel therapeutic strategies to promote hematoma resolution are needed. The present application will assess the potential for the clinically non-toxic curry spice, curcumin, to promote hematoma resolution and improve outcomes after ICH.