Ischemia Induced Plasticity - Implications for Therapy

缺血引起的可塑性 - 对治疗的影响

• 批准号: 6780361
• 负责人: JOEL H GREENBERG
• 金额: $ 30.12万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6780361
• 关键词: behavior test; behavioral /social science research tag; brain circulation; brain injury; brain metabolism; cerebral ischemia /hypoxia; disease /disorder model; functional ability; glucose metabolism; laboratory rat; medical rehabilitation related tag; neural plasticity; paired stimuli; rehabilitation; somesthetic sensory cortex; stroke; vibrissae

DESCRIPTION (provided by applicant): There is an evolving understanding that neuronal cortical connections can be altered and remodeled following injury to the central nervous system. Humans with stroke frequently show recovery of function that seems to be correlated with activation of regions both in the peri-infarct zone as well as in the hemisphere opposite to the stroke. Cerebral ischemic injury in animals is accompanied by hyperexcitability in tissue surrounding the ischemic core and frequently in homologous regions of the contralateral cortex. There is clinical and behavioral data showing that the degree of recovery can be altered using sensory augmentation including enriched environments and task-specific training. Recovery following chronic stroke can also be improved with pharmacological treatment, with the recovery dependent on activity during treatment. We will use hemodynamic image mapping to examine the reorganization of the brain following a focal cerebral ischemic insult and correlate this reorganization with behavioral recovery. Focal ischemia/reperfusion will be achieved using a compression model that results in ischemic damage confined to the posteriomedial barrel subfield of the first somatosensory cortex of the rat, and reorganization will be evaluated by examining the changes in the blood flow response maps to vibrissae stimulation. The mystacial vibrissae of the rat, with their corresponding representation in the somatosensory cortex, provides an ideal vehicle for studies dealing with damage and subsequent recovery in the central nervous system. Examination of how the brain reorganizes following ischemia/reperfusion to the rat barrel somatosensory cortex, as opposed to ablative injury, will provide valuable information about strategies for improving recovery following stroke. Strategies for altering reorganization of blood flow and metabolism that will be examined include administration of pharmacological agents and stromal cell, as well as targeted sensory augmentation.

描述（由申请人提供）：有一个不断发展的理解，神经元皮层连接可以改变和重建中枢神经系统损伤后。中风患者经常表现出功能的恢复，这似乎与梗死周围区域以及与中风相反半球的激活有关。动物脑缺血损伤伴有缺血核心周围组织和对侧皮层同源区域的高兴奋性。临床和行为数据表明，恢复的程度可以通过感官增强来改变，包括丰富的环境和特定任务的训练。慢性中风后的恢复也可以通过药物治疗得到改善，恢复取决于治疗期间的活动。我们将使用血流动力学图像映射来检查局灶性脑缺血损伤后大脑的重组，并将这种重组与行为恢复联系起来。局部缺血/再灌注将通过压缩模型来实现，该模型导致大鼠第一体感皮层后内侧桶状亚区局部缺血损伤，重组将通过检查刺激刺激后血流反应图的变化来评估。大鼠的神秘触须在体感觉皮层中具有相应的表征，为研究中枢神经系统的损伤和随后的恢复提供了理想的载体。检查缺血/再灌注到大鼠体感觉皮层后大脑如何重组，而不是消融性损伤，将为提高中风后恢复的策略提供有价值的信息。改变血流和代谢重组的策略将被检查，包括药物和基质细胞的管理，以及有针对性的感觉增强。