ASTROCYTE CA2+ DYNAMICS AND NEURONAL REMODELING IN EPILEPSY

星形胶质细胞 CA2 动力学和癫痫中的神经元重塑

• 批准号: 8167445
• 负责人: Mitsuhiro Morita
• 金额: $ 23.79万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167445
• 关键词: Address; Animal Model; Astrocytes; Brain; Brain Injuries; Caliber; Cells; Cephalic; Computer Retrieval of Information on Scientific Projects Database; Confusion; Craniotomy; Epilepsy; Focal Brain Injuries; Funding; Gliosis; Grant; Growth; Halogens; Head; Injury; Institution; Light; Microscope; Modeling; Morphologic artifacts; Mus; Natural regeneration; Nature; Nerve Degeneration; Neurons; Pathologic Processes; Population; Publications; Recovery; Reporting; Research; Research Personnel; Resources; Rodent; Role; Somatosensory Cortex; Source; Study models; Tissues; United States National Institutes of Health; cell type; clinically relevant; cranium; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aims and Results Massive growth of reactive astrocytes after focal brain injury suggests critical roles of this cell type in the progress of tissue degeneration and/or recovery. However, basic questions about postlesional reactive astrocytes, such as "Are reactive astrocytes neuroprotective or neurodegenerative?" and "Do reactive astrocytes promote or inhibit neuronal network regeneration?" are still to be addressed. The current confusion in postlesional reactive astrocyte studies is largely attributed to the lack of appropriate animal model. The gliosis in existing focal brain injury models are likely complicated by an experimental artifact. A recent publication reported that the large craniotomy, which is commonly used in brain injury models for creating focal and severe injury in small rodent brains, caused gliosis by itself (Xu et al, Nature Neuroscei. 2007). Thus, the reactive astrocytes, which are well recognized as heterogeneous cell population, in existing brain injury models reflect experimental artifacts, rather than clinically-relevant pathological processes. In order to overcome this problem, we established a novel brain injury model for studying functions of postlesional reactive astrocyte without the artifactual gliosis in Year 1. For this purpose, we created focal brain injury by the intense light exposure through thinned-skull cranial window, which did not cause the artifactual gliosis. Small skull region, which was large enough for focusing light in cortical tissue through 20x microscope objective (approximately 0.5 mm in diameter), was scraped for increasing light transmittance. By exposing cortical tissue to light from 90W halogen lamp, we successfully created severe brain injury in mouse somatosensory cortex in closed-head condition.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目标和结果 局灶性脑损伤后反应性星形胶质细胞的大量生长表明这种细胞类型在组织退化和/或恢复过程中发挥着关键作用。然而，关于病变后反应性星形胶质细胞的基本问题，例如“反应性星形胶质细胞是神经保护性的还是神经退行性的？”和“反应性星形胶质细胞促进还是抑制神经元网络再生？”仍有待解决。目前损伤后反应性星形胶质细胞研究的混乱很大程度上归因于缺乏合适的动物模型。现有局灶性脑损伤模型中的神经胶质增生可能因实验伪影而变得复杂。最近的一篇出版物报道说，大开颅手术通常用于脑损伤模型，在小型啮齿动物大脑中造成局灶性和严重损伤，但其本身会引起神经胶质增生（Xu 等人，Nature Neuroscei.2007）。因此，现有脑损伤模型中的反应性星形胶质细胞被公认为异质细胞群，反映的是实验假象，而不是临床相关的病理过程。为了克服这个问题，我们建立了一种新的脑损伤模型，用于研究第一年无人工神经胶质增生的病变后反应性星形胶质细胞的功能。为此，我们通过薄颅骨颅窗的强光照射造成局灶性脑损伤，这并没有引起人为的神经胶质增生。小头骨区域足够大，可以通过 20 倍显微镜物镜（直径约 0.5 毫米）将光聚焦在皮质组织中，被刮擦以增加透光率。通过将皮层组织暴露在 90W 卤素灯的光下，我们成功地在闭头状态下对小鼠体感皮层造成了严重的脑损伤。