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: 7959369
• 负责人: Mitsuhiro Morita
• 金额: $ 26.85万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959369
• 关键词: Animal Model; Astrocytes; Brain Injuries; Cell Culture Techniques; Commit; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Epilepsy; Functional disorder; Funding; Glial Fibrillary Acidic Protein; Goals; Grant; Institution; Natural regeneration; Neurons; Peripheral; Post-Traumatic Epilepsy; Process; Recovery; Recurrence; Research; Research Personnel; Resources; Signal Transduction; Source; Synapses; Therapeutic; Traumatic Brain Injury; United States National Institutes of Health; brain tissue; clinically relevant; improved; injured; novel; programs; synaptogenesis; therapeutic target

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 Astrocyte activation and recurrent network formation leading to epilepsy follow diverse brain injuries, however their connection is still to be determined. In cell culture, astrocytes are activated as indicated by the high level GFAP expression, and essential to the synapse formation between coexisting neurons. In traumatic brain injury (TBI), activated astrocytes up-regulate synapse formation and regenerate neuronal network, but they may also cause recurrent network formation and post-traumatic epilepsy (PTE). Therefore, it is clinically crucial to understand the process, through which activated astrocytes influence synapses. Since PTE develops after a long incubation period, ranging from weeks to years, the recovery from TBI can be improved, if appropriate diagnoses and therapeutic treatments are established for this period. However, the absence of an animal model clinically relevant to PTE has been a hamper for the progress in this field. The goal of this project is to establish a novel PTE animal model and to reveal the long term influence of the activated astrocytes to synapses in the injured brain tissue and the normal peripheral region. The specific aims are the followings; (1) Is there a specific astrocyte activation type which commits to recurrent network formation (a potential target for the initial diagnosis of PTE)? (2) What is the signal inducing the PTE type astrocyte activation (a potential therapeutic target for PTE)? (3) What is the astrocyte mechanism up-regulating synapse formation in injured brain tissue (a potential therapeutic target of PTE)?

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 星形胶质细胞激活和导致癫痫的反复网络形成伴随着多种脑损伤，但它们之间的联系仍有待确定。在细胞培养中，星形胶质细胞被激活，如高水平 GFAP 表达所示，这对于共存神经元之间的突触形成至关重要。在创伤性脑损伤（TBI）中，活化的星形胶质细胞上调突触形成并再生神经元网络，但它们也可能导致复发性网络形成和创伤后癫痫（PTE）。因此，了解激活的星形胶质细胞影响突触的过程在临床上至关重要。由于 PTE 是在长期潜伏期（从数周到数年）之后形成的，如果在此期间建立适当的诊断和治疗方法，TBI 的恢复可以得到改善。然而，缺乏与 PTE 临床相关的动物模型一直阻碍着该领域的进展。该项目的目标是建立一种新型的PTE动物模型，并揭示激活的星形胶质细胞对受损脑组织和正常外周区域突触的长期影响。具体目标如下； (1) 是否存在特定的星形胶质细胞激活类型导致反复网络形成（PTE 初步诊断的潜在目标）？ (2) 诱导PTE型星形胶质细胞激活的信号是什么（PTE的潜在治疗靶点）？ (3) 星形胶质细胞上调受损脑组织突触形成的机制是什么（PTE的潜在治疗靶点）？