Ischemic Injury and Neuroprotection in the Immature Brain

未成熟大脑的缺血性损伤和神经保护

• 批准号: 7229434
• 负责人: ANNE M COMI
• 金额: $ 17.61万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7229434
• 关键词: Ischemic; Injury; Neuroprotection; Immature; Brain

DESCRIPTION (provided by applicant): The career objective of this proposal is to permit the candidate, an academic child neurologist and recipient of a NINDS Neurological Scientist Academic Development Award (K12), to establish an independent research program in ischemic injury and neuroprotection in the immature brain. This Award would permit the candidate to characterize a highly promising animal model of stroke in the immature brain, develop expertise in endogenous stem cell proliferation after ischemia, and to gain facility in carrying out rigorous mouse trials of neuroprotection with anticonvulsants. Stroke in the term neonate or infant is an important cause of neurologic morbidity. Dr. Comi has developed a new immature mouse model of stroke utilizing unilateral carotid ligation alone to produce infarcts in immature mice. The vulnerability to injury varies with strain and age at surgery. We have shown in this model that dextromethorphan, an NMDA receptor antagonist with anticonvulsant actions, is neuroprotective. This research addresses the hypothesis that anticonvulsants will attenuate ischemic brain injury in the immature brain. The candidate's long term goal is rigorous pursuit of preclinical screening of neuroprotective strategies for ischemic injury in the developing brain and enhancement of the endogenous stem cell response after injury. The Specific Aims are to: 1) Characterize the evolution of brain injury and endogenous stem cell proliferation after unilateral carotid ligation. 2) Determine the extent of anticonvulsant neuroprotection. Stroke in the developing brain is an important cause of neurologic impairment that often persists into adulthood. An intervention providing even partial reduction of neurologic impairments would result in significant benefit both in terms of quality of life and decreased national healthcare costs. This work will provide important insights into the brain injury and regenerative response after stroke in this new immature mouse model and will test neuroprotective interventions with relevance to this population.

描述（由申请人提供）：该提案的职业目标是允许候选人，学术儿童神经科医生，并获得Ninds神经科学家学术发展奖（K12），以建立一项独立的缺血性损伤和神经保护方案。该奖项将使候选人能够表征不成熟大脑中急性中风模型，缺血后在内源性干细胞增殖方面发展专业知识，并在对抗惊厥药进行严格的神经保护剂进行严格的小鼠试验时获得了设施。新生儿或婴儿一词中的中风是神经系统发病率的重要原因。 COMI博士仅利用单侧颈动脉连接来开发了一种新的不成熟小鼠模型，仅在未成熟的小鼠中产生梗塞。损伤的脆弱性随着手术时的应变和年龄而异。我们在该模型中表明，具有抗惊厥作用的NMDA受体拮抗剂右美甲苯是神经保护作用。这项研究解决了以下假设：抗惊厥药会减轻未成熟大脑的缺血性脑损伤。候选人的长期目标是严格追求临床前筛查神经保护策略，以在发育中发育中的缺血性损伤和受伤后内源性干细胞反应增强。具体目的是：1）表征单侧颈动脉连接后脑损伤和内源性干细胞增殖的演变。 2）确定抗惊厥神经保护的程度。发育中的大脑中风是神经系统损害的重要原因，通常会持续到成年。一项干预措施甚至部分减少神经系统障碍将在生活质量和降低国家医疗保健成本方面带来重大利益。这项工作将在这种新的未成熟小鼠模型中对中风后脑损伤和再生反应的重要见解，并将测试与该人群相关的神经保护干预措施。