Development of the mouse Subarachnoid hemorrhage model

小鼠蛛网膜下腔出血模型的建立

基本信息

批准号：
6935335
负责人：
JOSHUA B BEDERSON
金额：
$ 7.84万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-15 至 2007-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6935335
关键词：
acute disease /disorder brain circulation cerebral ischemia /hypoxia enzyme activity genetically modified animals histology isozymes laboratory mouse model design /development nitric oxide nitric oxide synthase pathologic process subarachnoid hemorrhage subarachnoid space

项目摘要

DESCRIPTION (provided by applicant): A well-characterized mouse model of subarachnoid hemorrhage (SAH) that reproduces the pathophysiology of acute clinical SAH does not exist. Such a model would permit the use of transgenic technology to examine the contribution of genes and products that contribute to acute ischemic injury after SAH. The goal of this study is to develop/characterize a mouse model of SAH, and use it to study Nitric Oxide Synthase (NOS) knockouts during the acute phase of SAH. The hypothesis of this study is that an endovascular filament model of SAH in the mouse can be developed to study acute cerebral ischemia after SAH using transgenic technology. The Specific aims are 1) to develop the endovascular monofilament model of SAH in the mouse, 2) to characterized the pathophysiology of SAH in this model, and 3) to study NOS knockouts using the model. We previously developed the rat endovascular model of SAH that is used by other workers in this area. The mouse model will be developed using similar techniques adapted to the decreased size of this animal. Endpoints used in characterization of the mouse SAH model will include measurements of blood pressure, intracranial pressure, bilateral cerebral blood flow and histological measurements of the severity of SAH and the degree of vasoconstriction. The utility of a mouse model of SAH will be determined by using knock out mice for endothelial-, neuronal-, or inducible NOS. The contribution of each NOS isozyme to acute changes of Nitric Oxide (NO) levels after SAH will be assessed. This investigation will extend previous Findings from our laboratory using the rat SAH model. The long-term goal of this grant is to develop a mouse SAH model to study the contribution of genes and their products to ischemic cerebral damage during the eady phases of SAH. Significance: development of a mouse SAH model could lead to new therapeutic options against acute cerebral injury after SAH.

描述（由申请人提供）：不存在急性临床SAH的病理生理学的亚蛛网膜下腔出血（SAH）的特征良好的小鼠模型。这种模型将允许使用转基因技术检查SAH后急性缺血性损伤的基因和产品的贡献。这项研究的目的是开发/表征SAH的小鼠模型，并使用它在SAH的急性期研究一氧化氮合酶（NOS）敲除。这项研究的假设是，可以开发出小鼠中SAH的血管内细丝模型，以研究SAH使用转基因技术后研究急性脑缺血。具体目的是1）在小鼠中开发SAH的内血管内单丝模型，2）表征SAH的病理生理学，以及3）使用该模型研究NOS敲除。我们以前开发了SAH的大鼠血管内模型，该模型被该领域的其他工人使用。小鼠模型将使用适合该动物尺寸减小的类似技术开发。用于表征小鼠SAH模型的终点将包括血压的测量，颅内压，双侧大脑血流以及SAH严重程度的组织学测量以及血管收缩程度。 SAH小鼠模型的效用将通过将小鼠用于内皮，神经元或诱导的NOS来确定。每个NOS同工酶对SAH后一氧化氮水平的急性变化（NO）的贡献将评估。这项调查将使用大鼠SAH模型从我们实验室的先前发现。该赠款的长期目标是开发小鼠SAH模型，以研究SAH阶段期间基因及其产物对缺血性脑损伤的贡献。意义：SAH模型的开发可能导致SAH后针对急性脑损伤的新治疗选择。