OBSERVATION ON BRAIN-DERIVED NEUROTROPHIC FACTOR IN CEREBRAL ISCHEMIA

脑缺血中脑源性神经营养因子的观察

• 批准号: 3760387
• 负责人: N KAWAHARA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3760387
• 关键词: cerebral ischemia /hypoxia; gamma aminobutyrate; heart arrest; immunocytochemistry; laboratory rat; nervous system regeneration; neurogenesis; neuronal guidance; neuroprotectants; neurotrophic factors; pons; spreading cortical depression; stereotaxic techniques; thalamic nuclei

Our studies have generally been focused on the nature of defensive and regenerative mechanisms which can be activated in response to ischemic injury, as well as on potential therapeutic manipulation of such defensive responses. In these studies we were able to demonstrate participation of brain-derived neurotrophic factor (BDNF) in the development of enhanced neuronal resistance to ischemic injury, demonstrable 3 days after induction of the spreading depression in the cortex. In therapeutic trials, BDNF was administered via the microcanullae inserted sterotaxically into the ventral thalamic region of the rat subjected to cardiac arrest cerebral ischemia (CACI). The delivery of the BDNF commenced 3 days before the CACI and lasted till the sacrifice of the animal at 7 days after cardiac arrest. Using specific monoclonal antibody for GABA demonstrated a striking proliferation and sprouting of GABAergic terminals in the ventral thalamic nucleus in the vicinity of the site of BDNF delivery. Also, there was a conspicuous preservation of GABAergic neurons of the nucleus reticularis thalami on the side of BDNF application.

我们的研究一般都集中在防御性和 可被激活以应对缺血的再生机制 损伤，以及这种潜在的治疗操作 防御性反应。在这些研究中，我们能够证明 脑源性神经营养因子在脑缺血再灌注损伤中的作用 增强神经元对缺血损伤的抵抗力， 可在诱发弥漫性抑郁3天后表现出来 大脑皮层。在治疗试验中，脑源性神经营养因子通过 经立体定向植入丘脑腹侧区的微管 对心脏骤停脑缺血(CACI)大鼠的影响。这个 BDNF的交付在CACI前3天开始，一直持续到 在心脏骤停后7天处死动物。使用特定的 抗GABA的单抗表现出显著的增殖和 大鼠丘脑腹侧核内GABA能终末的萌发 BDNF投放地点附近。此外，还有一个明显的 大鼠丘脑网状核GABA能神经元的保存 脑源性神经营养因子应用方面。