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)?
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