Cerebral Blood Flow Response to Chronic Hydrocephalus

慢性脑积水的脑血流反应

• 批准号: 6529709
• 负责人: Mark Gregory Luciano
• 金额: $ 35.7万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 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 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6529709
• 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（由申请人提供）：慢性成人脑积水是一种主要的 可预防的神经损伤的原因。尽管其病理生理学 对诊断和治疗知之甚少，很可能是大脑缺氧， 通过血管压缩，在这种损伤中发挥作用。我们首先假设 最初的机械脑血流 (CBF) 妥协是较晚的 通过适应性血管生成来延缓，而适应性血管生成是由缺氧刺激演变而来的 血管生成因子。我们的第二个一般假设指出，脑脊髓 液体（CSF）分流可部分恢复 CBF 和氧气水平，但这样做 逆转适应性血管生成。我们开发了慢性病犬模型 脑积水，可以测量心室大小和压力， 它们与血管分布、脑血流量和氧气输送的关系 大脑。实验动物和对照动物将进行为期 12 周的研究 第2阶段，将被分流。测量包括临床状态、心室大小、 脑脊液压力、定量局部血管形态（密度、大小、面积）、 免疫组化（HIF-1、VEGF、GFAP）、脑血流 （多微球注射）和氧气水平（微氧传感器）。这 研究将首次确定慢性缺氧的作用和机制 脑积水。如果出现缺氧状态并提出脑血管反应 已证明，基于脑血管操纵或 神经保护可能被建议作为手术分流和分流的辅助手段 本身优化了。突然分流功能障碍可能导致继发性损伤 被最小化。具有更多生理引导的脑脊液引流和辅助 基于脑血流的治疗成人慢性病的治疗 脑积水的发病率将大大提高，神经系统的发病率也会降低。 最后，从这些研究中获得的见解可能有更广泛的应用 其他涉及逐渐压迫或缺氧的神经病理学。