ASTROCYTE CA2+ DYNAMICS AND NEURONAL REMODELING IN EPILEPSY

这个子项目是许多利用 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 星形胶质细胞激活和导致癫痫的复发性网络形成遵循不同的脑损伤，但它们的联系仍有待确定。在细胞培养中，星形胶质细胞被激活，如高水平GFAP表达所示，并且对于共存神经元之间的突触形成是必需的。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的发展经过一个长的潜伏期，从几周到几年不等，从TBI的恢复可以改善，如果适当的诊断和治疗，建立了这一时期的治疗。然而，缺乏临床相关的动物模型PTE一直是该领域的进展的障碍。本课题的目的是建立一种新的PTE动物模型，并揭示活化的星形胶质细胞对损伤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活化类型，其致力于复发性网络形成（PTE初步诊断的潜在靶点）？(2)诱导PTE型星形胶质细胞活化（PTE的潜在治疗靶点）的信号是什么？(3)星形胶质细胞上调受损脑组织中突触形成的机制是什么（PTE的潜在治疗靶点）？

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)?