It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in α-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that—given CSD probably exists in humans during migraine—spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.
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