Enhanced Microdialysis for CSD Monitoring

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 DESCRIPTION (provided by applicant): Brain injury gives rise to the phenomenon of cortical spreading depression. In healthy brain, spreading depressions are associated with migraine but are not known to cause brain damage. In the injured brain, recurrent spreading depressions lead to secondary brain injury and correlate significantly with poor patient outcomes including death, vegetative state, or severe disability 6 months after the primary injury. Microdialysis in patients with brain injury shows that spreading depressions deplete brain glucose, reflecting the sudden and intense demand for energy to drive ATP-dependent repolarization of brain tissue after the depolarization wave passes. Glucose delivery via the blood flow fails to keep pace with the demand and brain tissue becomes glucose deprived. This glucose deprivation is implicated in secondary injury to the at-‐risk penumbral tissue, resulting in expansion of the injury core. At present, clinical microdialysis is not used to assess the metabolic severity of spreading depressions due to variability in the results. The objective of this project is to develop, in experimental animals, "dexamethasone-enhanced microdialysis" as an approach to eliminate ischemia and gliosis at the microdialysis probe site and thereby improve the reliability of microdialysis measurements over the 1-10 day clinically relevant time window post-injury.