Location: Fields Institute
, 222 College Street, Toronto
Directions to Fields
April 17, 2009 --3:30
Robert M. Miura, New Jersey Institute of Technology
Migraine with Aura:
Treat It with Math
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 many
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.
I believe we can learn a lot about the brain by
studying extreme phenomena, and one such phenomenon
is CSD. 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. It 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. In this talk,
I will review some of the characteristics of CSD
wave propagation, and describe some of the mechanisms
that are believed to be important, including ion
diffusion, membrane ionic currents, osmotic effects,
the spatial buffer mechanism, neurotransmitter substances,
gap junctions, metabolic pumps, and synaptic connections.
Continuum models of CSD, consisting of coupled nonlinear
diffusion equations for the ion concentrations,
will be described.