title: Minimum conditions for the induction of cortical spreading depression in brain slices.
abstract: Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma.
authors.affiliation: Department of Mechanical and Aerospace Engineering and Department of Bioengineering, University of California, Los Angeles, California;
authors.forename: Yujie T
authors.initials: YT
authors.lastname: Tang
authors.affiliation: Department of Neurology, University of Utah, Salt Lake City, Utah; and.
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Mendez
authors.affiliation: Department of Neurology, University of Utah, Salt Lake City, Utah; and.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Theriot
authors.affiliation: Department of Neurology, University of Utah, Salt Lake City, Utah; and.
authors.forename: Punam M
authors.initials: PM
authors.lastname: Sawant
authors.affiliation: Department of Neurology, University of California, Los Angeles, California.
authors.forename: Héctor E
authors.initials: HE
authors.lastname: López-Valdés
authors.affiliation: Department of Mechanical and Aerospace Engineering and Department of Bioengineering, University of California, Los Angeles, California;
authors.forename: Y Sungtaek
authors.initials: YS
authors.lastname: Ju
authors.affiliation: Department of Neurology, University of Utah, Salt Lake City, Utah; and k.c.brennan@hsc.utah.edu.
authors.forename: K C
authors.initials: KC
authors.lastname: Brennan
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D003198:Computer Simulation; D013181:Cortical Spreading Depression / Q000502:physiology*; D004867:Equipment Design; D005110:Extracellular Space / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D008959:Models, Neurological; D061848:Optical Imaging; D011188:Potassium / Q000378:metabolism*; D046509:Tissue Culture Techniques / Q000295:instrumentation
chemical_list: D011188:Potassium
keywords: cortical spreading depression; microfluidics; migraine