In people who suffer from migraine with aura, splitting headaches are often preceded by cortical spreading depression (SD), a wave of neuronal excitation and prolonged depolarization that progressively renders brain tissue inactive.
Studies have suggested that the epilepsy drug pregabalin might help treat migraine with aura, but the drug’s efficacy remains unestablished.
Using live brain imaging, researchers. examined the drug’s effects on mouse models of mild and severe forms of familial hemiplegic migraine (FHM1), which is caused by distinct mutations in a subunit of a voltage-gated calcium channel.
SD reached the brain’s striatum and hippocampus in both forms of the disease, with the mild form displaying a delayed effect; the cerebellum was spared in wild-type and mutant mice. Pregabalin, which binds to the α2δ1 subunit of CaV2.1 calcium channels, raised the threshold of SD initiation in wild-type but not FHM1 mutant mice.
Conversely, the drug slowed SD spread in FHM1 but not wild-type mice, and prevented the wave from invading the brain’s subcortical structures in the mild but not the severe form of the disease.
Moreover, the drug attenuated synaptic activity in CA1 neurons in hippocampal slices from wild-type mice and mice with the mild mutation. According to the authors, pregabalin might represent a potential treatment for mild forms of FHM1 as well as noncongenital migraine.
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