Therapeutic targeting of CD36 after intracerebral hemorrhage

脑出血后 CD36 的治疗靶向

• 批准号: 8432013
• 负责人: KRISHNAN M. DHANDAPANI
• 金额: $ 18.09万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8432013
• 关键词: Accounting; Acute; Address; American; Biochemical; Blood Clot; Blood Vessels; Blood coagulation; Brain; Brain hemorrhage; CCAAT-Enhancer-Binding Proteins; CD36 gene; Cerebral hemisphere hemorrhage; Clinical; Clinical Management; Coagulation Process; Curcumin; Data; Deterioration; Development; Diabetes Mellitus; Dose; Erythrocytes; Genetic; Goals; Hematoma; Hemorrhage; Human; Hypertension; Incidence; Intervention; Knowledge; Laboratories; Lesion; Location; Mediating; Mediator of activation protein; Medical; Microglia; Modeling; Molecular; Molecular Weight; Morbidity - disease rate; Mus; Nervous System Trauma; Neurologic; Neurological outcome; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Pattern; Phagocytosis; Pharmacologic Substance; Research; Resolution; Risk Factors; Rodent; Role; Rupture; SR-B proteins; Serum; Spices; Stroke; Testing; Therapeutic; aging population; base; brain tissue; clinical care; clinical practice; demographics; improved; mortality; neuroimaging; novel; novel therapeutics; pre-clinical; therapeutic target; transcription factor

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.

描述（由申请人提供）：脑出血（ICH）是出血性卒中的最常见形式，占所有卒中的15%，每年有37，000 - 52，400名美国人患有ICH。在所有类型的卒中中，ICH的急性死亡率最高，长期神经系统结局最差。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较高的死亡率相关;然而，许多ICH患者是不佳的手术候选者和/或存在不利的病变大小/位置，限制了神经外科干预的效用。此外，缺乏促进血肿清除的有效药物治疗选择，这对临床实践构成了关键障碍。我们的长期目标是确定分子和细胞途径， 有助于ICH后凝块消退。这些知识将为药物开发提供一个框架，以改善ICH后的患者结局。我们的试验数据表明，咖喱香料，姜黄素，促进脑出血后血肿的解决，因此可能代表一种新的和安全的治疗选择。具体目标1将检验CD 36介导姜黄素诱导的ICH后血肿清除的假设。具体目标2将检验C/EBP-â介导姜黄素诱导的CD 36表达和ICH后血肿消退的假设。总之，拟议的研究将阐明姜黄素促进血肿消退能力的分子和细胞机制。这些研究的结果将为靶向C/EBP-1和/或CD 36的药物开发提供框架，以改善ICH后的临床结局。