| Abstract | Migraine with aura (classic migraine) is a debilitating disease that affects people around the world. The triggers of this condition are various and undiagnosed in most cases, and treatments are essentially ad hoc on a patient-by-patient basis. Migraine with aura has been linked to waves of cortical spreading depression (CSD) in the visual cortex of the brain. In spite of an enormous experimental and theoretical literature on the brain, we do not have a good understanding of how it functions on a gross mechanistic level. To devise rational treatments for migraine with aura, much more needs to be known about the brain and about CSD. In general, the brain maintains a homeostatic state with relatively small ion concentration changes, the major ions being sodium, potassium, and chloride, and a very important ion, calcium. We can learn a lot about the brain by studying extreme phenomena, and CSD is such a phenomenon. CSD was discovered 65 years ago by A.A.P. Leão, a Brazilian physiologist during his PhD research on epilepsy at the Harvard Medical School. CSD is characterized by nonlinear chemical waves that propagate at very slow speeds, on the order of mm/min, in the cortex of different brain structures in various animals, including humans. CSD waves generate massive changes in extracellular ion concentrations, but to date, we do not have a good explanation of how CSD occurs, although a number of mechanisms have been hypothesized to be important for CSD wave propagation. Some of these mechanisms are ion diffusion, membrane ionic currents, neurotransmitter substances, gap junctions, metabolic pumps, synaptic connections, osmotic effects, and the spatial buffer mechanism. In this talk, I will review some of the characteristics of CSD wave propagation, and describe some of the above mechanisms. Continuum models of CSD, consisting of coupled nonlinear diffusion equations for the ion concentrations, will be described. |
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