A NEW PEDIATRIC MODEL OF ISCHEMIC STROKE IN PIGLETS

仔猪缺血性中风的新儿科模型

• 批准号: 6871336
• 负责人: John Wallace Kuluz
• 金额: $ 17.99万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6871336
• 关键词: angiogenesis; apoptosis; brain injury; cerebral artery; cerebral ischemia /hypoxia; cerebrovascular occlusions; confocal scanning microscopy; disease /disorder model; immunocytochemistry; infant animal; infarct; leukocyte activation /transformation; magnetic resonance imaging; method development; pediatrics; stroke; swine

DESCRIPTION (provided by applicant): Ischemic stroke is a serious yet poorly studied problem in infants and children with a variety of acute and chronic illnesses. In spite of this, stroke in the immature brain has received little attention in basic science research. One reason for this is the lack of feasible animal models, which closely mimic the clinical picture of pediatric stroke. From the few studies that have been done in immature animal models, it appears that there are age-related differences in the mechanisms of focal ischemic injury in the brain. These mechanistic differences suggest that treatment strategies to reduce ischemic brain injury may need to be different in the immature compared to the mature brain. We recently developed a large animal model of ischemic stroke in two- to four-week-old infant piglets using a transorbital approach to produce photothrombotic occlusion of the middle cerebral artery. We measured acute changes in regional cerebral blood flow, examined histopathology at four hours after stroke onset and demonstrated that this method produces a moderate size infarct, which includes both cortical and subcortical tissue. The purpose of this exploratory project is to further establish this model of ischemic stroke in piglets at different stages of development for future investigations of age-related mechanisms of injury, repair and response to therapeutic interventions. The specific aims are (1) to improve our method of producing stroke so that chronic survival is achieved in pigs at three stages of development, (2) to determine age-related differences in regional cerebral blood flow, size of the infarct, functional neurological outcome and magnetic resonance imaging twenty-fours hours and three, seven and thirty days after stroke onset, and (3) To explore whether age-related and time-dependent differences occur in three mechanisms of injury and repair after stroke, e.g., leukocyte accumulation, angiogenesis and apoptosis. This study is important because there are no large animal models of pediatric stroke, which include chronic survival to allow for investigations of age-related mechanisms of and recovery from ischemic brain injury. The results of these experiments will demonstrate whether, in fact, the immature brain recovers from stroke more rapidly and more completely than the adult brain and provide insight into which injury and repair mechanisms are responsible for the improved outcome from stroke during development.

描述（由申请人提供）：缺血性卒中是一个严重但研究良好的问题，患有多种急性和慢性病的儿童。尽管如此，在基础科学研究中，未成熟大脑中的中风很少受到关注。原因之一是缺乏可行的动物模型，这些模型紧密模仿了小儿中风的临床图片。从未成熟动物模型中进行的少数研究中，看来大脑局灶性缺血性损伤机理存在差异。这些机械差异表明，与成熟的大脑相比，减少缺血性脑损伤的治疗策略可能需要不同。我们最近使用透明质方法在两到四周大的婴儿小猪中开发了一种大型的缺血性卒中动物模型，以产生大脑中动脉的光胰弥漫性闭塞。我们测量了局部脑血流的急性变化，在中风发作后四个小时检查了组织病理学，并证明该方法会产生中等大小的梗塞，其中包括皮质和皮质下组织。该探索性项目的目的是进一步建立这种缺血性中风的模型，在开发的不同阶段的仔猪中，以未来研究与年龄相关的损伤，修复和对治疗干预措施的反应。 （1）的具体目的是改善我们的中风方法，以便在三个发育阶段的猪中实现慢性存活，（2）确定与年龄相关的脑血流，梗塞大小，功能性神经学结果的大小，功能性神经学结果和磁性差异，并在二十四个小时和二十四个小时，二十四个和the neepertirest和the ecrove and eccomptirent和the eccomptirent，以及（3岁），以及（3），以及（3），以及3个阶段（3）。中风后的三种损伤和修复机制发生，例如白细胞积累，血管生成和凋亡。这项研究很重要，因为没有大型的小儿中风动物模型，其中包括慢性存活，以便研究与年龄相关的机制和缺血性脑损伤的恢复。这些实验的结果将证明，实际上，未成熟的大脑是否比成人大脑更快，更完全地从中风中恢复过来，并提供有关在发育过程中造成损伤和修复机制导致中风的结果改善的洞察力。