Cerebral Blood Flow Response to Chronic Hydrocephalus

慢性脑积水的脑血流反应

• 批准号: 6651041
• 负责人: Mark Gregory Luciano
• 金额: $ 34.43万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651041
• 关键词: angiogenesis; brain circulation; cerebral ischemia /hypoxia; cerebrospinal fluid; chronic disease /disorder; disease /disorder model; dogs; hydrocephalus

DESCRIPTION (provided by applicant): Chronic adult hydrocephalus is a leading cause of preventable neurological injury. Although its pathophysiology, diagnosis, and treatment are poorly understood it is likely that brain hypoxia, through vessel compression, plays a role in this injury. We first hypothesize that an initial mechanical cerebral blood flow (CBF) compromise is later temporized by adaptive angiogenesis, which evolves from hypoxia stimulated angiogenic factors. Our second general hypothesis states that cerebral spinal fluid (CSF) shunting partially restores CBF and oxygen level but in so doing reverses the adaptive angiogenesis. We have developed a canine model of chronic hydrocephalus, which allows measurement of ventricular size and pressure and their relationship to vascularity, cerebral blood flow, and oxygen delivery to the brain. Experimental and control animals will be studied for 12 weeks and in phase 2, will be shunted. Measurements include clinical status, ventricle size, CSF pressure, quantitative regional vessel morphology (density, size, area), immunohistochemistry (HIF-1, VEGF, GFAP), cerebral blood flow (multi-microsphere injections), and oxygen level (micro oxygen sensor). This study will be the first to identify the role and mechanism of chronic hypoxia in hydrocephalus. If the hypoxic state and proposed cerebrovascular response are demonstrated, strategies based on cerebrovascular manipulation or neuroprotection may be proposed as adjuncts to surgical shunting and shunting itself optimized. Secondary injury resulting from sudden shunt dysfunction may be minimized. With more physiological guided CSF drainage and adjunct treatments based on cerebral blood flow our treatment of adult chronic hydrocephalus would be greatly enhanced and its neurological morbidity reduced. Finally, the insights gained from these studies may have a broader application to other neuropathologies involving gradual compression or hypoxia.

描述（申请人提供）：慢性成人脑积水是一种领先的