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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目标和成果 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变性和/或恢复的进展中起关键作用。然而，关于损伤后反应性星形胶质细胞的基本问题，如“反应性星形胶质细胞是神经保护性的还是神经变性的？反应性星形胶质细胞促进或抑制神经元网络再生吗？“仍有待解决。目前损伤后反应性星形胶质细胞研究的混乱主要是由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复杂化。最近的出版物报道，通常用于脑损伤模型中以在小啮齿动物脑中产生局灶性和严重损伤的大开颅术本身引起神经胶质增生（Xu等人，Nature Neuroscei. 2007年）。因此，反应性星形胶质细胞，这是公认的异质细胞群体，在现有的脑损伤模型中反映实验的假象，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，用于研究损伤后反应性星形胶质细胞的功能，而在第1年没有人为的胶质细胞增生。为此，我们通过薄颅骨颅窗用强光照射造成局灶性脑损伤，但不引起人工胶质细胞增生。刮擦小颅骨区域，其足够大以通过20倍显微镜物镜（直径约0.5 mm）将光聚焦在皮质组织中，以增加透光率。采用90 W卤素灯照射小鼠皮层，成功地造成了小鼠头部封闭条件下躯体感觉皮层的严重脑损伤。