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Publications in VIVO

Shuttleworth, Bill Regents' Professor


Our laboratory is currently focused almost entirely on spreading depolarization (SD) events, which are profound depolarizations of neurons and glia that propagate slowly throughout the brain. A colloquial term for these events is "Brain Tsunamis" (click here to see a short introductory video about brain tsunamis).  There has been a resurgence in interest in SD, as recent clinical recordings have implicated SDs as key contributors to progression of acute brain injuries (including stroke and traumatic brain injury).   The long-term goal of our lab is to help develop SD interventions that can be applied at late time points, and which ultimately will be translatable to the clinic. We use brain slices and animal models to identify 1) fundamental mechanisms that underlie damaging effects of SD, and 2) approaches to support compromised tissues to recover from repeated SD episodes. Recent studies include the regulation of SD by waves of synaptic zinc release, and discovery of an unexpected increase in glutamate release immediately following the passage of the SD wave-front. Excessive NMDA receptor activation during this limited time window can be sufficient to explain neuronal injury following SD in metabolically compromised tissues.  A challenge now is to determine the relative contribution of pre- and post-synaptic mechanisms, and to identify the most useful targets of intervention.    In parallel, we are also studying mechanisms regulating metabolic supply and recovery from SD.  These efforts include studies of neurovascular coupling, and markers of metabolic depletion to identify tissues at risk of injury following SD in compromised brain.