IN VIVO IMAGING OF SEIZURE-INDUCED ASTROCYTIC INJURY

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 DESCRIPTION (provided by applicant): Epilepsy is often associated with disabling comorbidities, including cognitive impairment, psychiatric and behavioral disorders, and other neurological deficits. Seizures themselves may cause brain injury, which might, in part, contribute to these comorbid conditions, as well as promote a progressive process of epileptogenesis leading to worsening seizures. Although neurons remain the principal cells mediating epilepsy and its comorbidities, the role of glia in regulating epileptogenesis and associated brain injury has become increasingly recognized. Recent advances with in vivo imaging demonstrate that astrocytes undergo rapid, dynamic structural changes under a variety of physiological and pathological conditions, including neuronal activity-dependent modulation. However, minimal information is available on rapid, dynamic changes in astrocytes occurring in epileptic states. The primary hypothesis of this research proposal is that seizures cause acute, dynamic structural changes in astrocytes, which correlate with injury to neighboring dendrites. In this grant, we will utilize in vivo multiphoton imaging to assess both the acute and evolving chronic effects of kainate-induced seizures on cortical astrocytes in mice. This proposal is innovative in applying cutting-edge in vivo imaging methods for studying seizure-induced brain injury. This work also has strong clinical significance, as it will lay the foundation for dissectig the underlying mechanistic basis of seizure-induced glial injury and testing rational therapeutic interventions for epilepsy targeting astrocytes.