Ischemia Induced Plasticity - Implications for Therapy

描述（由申请人提供）：有一种不断发展的理解，即中枢神经系统损伤后神经元皮质连接可以改变和重塑。患有中风的人经常表现出功能恢复，这似乎与梗塞周围区以及中风相对半球中的区域的激活相关。动物的脑缺血性损伤伴随着缺血核心周围组织的过度兴奋，并且经常出现在对侧皮质的同源区域。有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来改善，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相关联。使用压缩模型实现局灶性缺血/再灌注，该模型导致局限于大鼠第一躯体感觉皮层的后内侧桶形子区域的缺血性损伤，并通过检查对触须刺激的血流反应图的变化来评价重组。大鼠的触须肌及其在躯体感觉皮层中的相应表达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。与烧蚀性损伤相比，对大鼠桶状体感皮层缺血/再灌注后大脑如何重组的研究将为改善卒中后恢复的策略提供有价值的信息。改变血流重组和代谢的策略将被检查，包括药物制剂和基质细胞的管理，以及有针对性的感觉增强。

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.