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.
Brain injury, including but not limited to traumatic brain injury, is an epidemic with 1.7 million cases of TBI annually in the US, resulting in 53,000 deaths. Spreading depression events are implicated in poor patient outcomes, including death, vegetative state, and severe disability 6-months after injury. The inability to assess the metabolic severity of spreading depressions hinders patient care and the development of brain injury therapies. The goal of this project is to develop 'dexamethasone?enhanced microdialysis' to address this technological gap.
| Varner, Erika L; Leong, Chi Leng; Jaquins-Gerstl, Andrea et al. (2017) Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization. ACS Chem Neurosci 8:1779-1788 |
