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）：慢性成人脑积水是领先的 可预防的神经损伤的原因。尽管它的病理生理学，但 诊断和治疗知之甚少，大脑缺氧很可能 通过血管压缩，在这种伤害中起作用。我们首先假设 初始的机械脑血流（CBF）妥协较晚 由自适应血管生成暂时，从缺氧刺激的缺氧演变 血管生成因子。我们的第二个一般假设指出脑脊柱 流体（CSF）分流部分恢复CBF和氧气水平，但这样做 逆转自适应血管生成。我们已经开发了慢性犬模型 脑积水，可以测量心室尺寸和压力，并且 它们与血管性，脑血流量和氧气的关系 大脑。实验和对照动物将研究12周，并在 第2阶段将分流。测量包括临床状态，心室大小， CSF压力，定量区域血管形态（密度，大小，面积）， 免疫组织化学（HIF-1，VEGF，GFAP），脑血流 （多微球注射）和氧气水平（微氧传感器）。这 研究将是第一个确定慢性缺氧的作用和机制的研究 在脑积水中。如果缺氧状态和拟议的脑血管反应 证明了基于脑血管操纵或 神经保护可以作为手术分流和分流的辅助 本身优化。突然分流功能障碍造成的继发伤害可能 最小化。具有更多生理指导的CSF排水和辅助 基于脑血流的治疗方法我们的成人慢性治疗 脑积水将大大增强，其神经系统发病率降低。 最后，从这些研究中获得的见解可能具有更广泛的应用 涉及涉及逐渐压缩或缺氧的其他神经病理学。