Cortical spreading depression can be triggered by sensory stimulation in primed wild type mouse brain: a mechanistic insight to migraine aura generation

Background Unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain. Methods Cortex was made susceptible to CSD with partial inhibition of Na + /K + -ATPase by epidural application of a low concentration of Na + /K + -ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down α2 subunit of Na + /K + -ATPase, which is crucial for K + and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K + changes were monitored in vivo electrophysiologically and a K + -sensitive fluoroprobe (IPG-4), respectively. Results After priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p