Therapeutic targeting of CD36 after intracerebral hemorrhage

描述（由申请人提供）：脑出血（颅内出血）是出血性中风最常见的形式，占所有中风的15%，每年有37,000-52,400名美国人患有颅内出血。脑出血在所有类型的中风中具有最高的急性死亡率和最糟糕的长期神经预后。脑出血是由脑内血管破裂引起的，导致形成占位性血肿。血肿体积在临床上与神经功能恶化和更高的死亡率相关；然而，许多脑出血患者不适合手术治疗和/或病变的大小/位置不利，限制了神经外科干预的应用。此外，缺乏有效的药物治疗方案来促进血肿清除，这是临床实践的一个关键障碍。我们的长期目标是确定分子和细胞途径

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.