Center for Brain Hemorrhage Research

脑出血研究中心

• 批准号: 8993925
• 负责人: John H Zhang
• 金额: $ 122.57万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8993925
• 关键词: Address; Animal Model; Arteries; Astrocytes; Basal Ganglia; Behavioral; Biological Neural Networks; Biology; Blast Injuries; Blood - brain barrier anatomy; Blood Vessels; Blood coagulation; Brain; Brain Edema; Brain Injuries; Brain hemorrhage; Brain region; Caveolins; Cell Death; Cerebral Ischemia; Cerebral Ventricles; Cerebral hemisphere hemorrhage; Cerebrum; Chemicals; Cognitive deficits; Coin; Comparative Study; Disabled Persons; Disease; Endothelial Cells; Event; Exhibits; Functional disorder; Gleevec; Growth Factor Gene; Growth Factor Receptors; Head; Hematoma; Hemorrhage; Hemorrhagic Disorders; Hospital Mortality; Hypertension; Injury; Intracranial Pressure; Intracranial Sinus Thrombosis; Lead; Literature; Mechanics; Memory; Modeling; Neurologic; Neurons; PDGFRB gene; Patients; Pericytes; Permeability; Phenotype; Physiology; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor Receptor; Program Research Project Grants; Proteins; Receptor Signaling; Recruitment Activity; Research; Rodent Model; Rupture; Ruptured Aneurysm; Services; Signal Pathway; Signal Transduction; Site; Smooth Muscle; Smooth Muscle Myocytes; Spasm; Sports; Subarachnoid Hemorrhage; Subarachnoid Space; Surface; Survivors; Therapeutic; Tissues; Traumatic Brain Injury; Veins; arteriole; base; brain tissue; caveolin 1; cerebral artery; cerebrovascular; combat; falls; feeding; improved; improved outcome; killings; mortality; neurobehavioral; neurobehavioral test; neuroimaging; neurosurgery; neurovascular; neurovascular injury; neurovascular unit; osteopontin; prevent; programs; public health relevance; response; treatment strategy; vehicular accident; venous sinus; venule

DESCRIPTION (provided by applicant): This Program Project Grant (PPG) will address how an "expanded neurovascular unit" responds to injury and putative therapeutic treatment in three major brain hemorrhagic disorders seen in neurosurgery service. The expanded neurovascular unit includes not only endothelial cells, pericytes, and astrocytes but also the feeding and upstream cerebral arteries of the neurovascular unit and arterial smooth muscle cells. The responses of the expanded neurovascular unit to hemorrhagic brain injury may not only demonstrate universal but also distinct pathophysiological features. In our PPG we propose a horizontal comparative study in rodent models o f t h e three major brain hemorrhage disorders, subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and traumatic brain injury (TBI). Similarly we will compare three different treatment strategies such as osteopontin (OPN), anti-PDGF (Gleevec), and AP-Cav (caveolin) in all three distinct hemorrhagic brain injury models. Based upon existing literature combined with our own preliminary observations, our hypothesis is that there are universal but distinct features of injury encompassing the expanded neurovascular unit following brain hemorrhage in SAH/ICH/TBI models. We further hypothesize that three distinct neurovascular protection strategies targeting the matrix protein OPN, PDGF-receptors, and endothelial caveolin will prevent arterial smooth muscle phenotype changes, provide neurovascular protection to strengthen blood-brain barrier (BBB) integrity, improve vascular function and reduce brain edema via different mechanisms.

描述（由申请人提供）：该计划项目资助（PPG）将解决“扩展神经血管单元”如何对神经外科服务中发现的三种主要脑出血性疾病的损伤和推定治疗做出反应。扩张的神经血管单位不仅包括内皮细胞、周细胞和星形胶质细胞，而且还包括神经血管单位的供血动脉和上游脑动脉以及动脉平滑肌细胞。扩张的神经血管单位对出血性脑损伤的反应不仅具有普遍性，而且具有不同的病理生理学特征。在我们的PPG中，我们提出了在三种主要脑出血疾病（蛛网膜下腔出血（SAH）、脑内出血（ICH）和创伤性脑损伤（TBI））的啮齿动物模型中进行横向比较研究。同样，我们将在所有三种不同的出血性脑损伤模型中比较三种不同的治疗策略，如骨桥蛋白（OPN）、抗PDGF（格列卫）和AP-Cav（小窝蛋白）。根据现有文献并结合我们自己的初步观察，我们的假设是，在SAH/ICH/TBI模型中，脑出血后扩大的神经血管单元周围存在普遍但独特的损伤特征。我们进一步假设三种不同的神经血管保护策略靶向基质蛋白OPN，PDGF受体和内皮小窝蛋白将防止动脉平滑肌表型变化，提供神经血管保护，以加强血脑屏障（BBB）的完整性，改善血管功能，并通过不同的机制减少脑水肿。