In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures

Autor: Barry Bohnet, Brian A. MacVicar, Terrance P. Snutch, Andrew Yung, John R. Tyson, Jeffrey M. LeDue, Huili Han, Esperanza Garcia, Piotr Kozlowski, Sascha R.A. Alles, Stuart M. Cain, Arn M. J. M. van den Maagdenberg
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cerebellar Ataxia
Migraine Disorders
Migraine with Aura
Pregabalin
Gene Expression
Mice
Transgenic
Pharmacology
Neurotransmission
Synaptic Transmission
familial hemiplegic migraine type 1
03 medical and health sciences
Mice
0302 clinical medicine
Calcium Channels
N-Type
In vivo
Commentaries
medicine
Edema
Animals
Humans
migraine
Familial hemiplegic migraine
Cerebral Cortex
Neurons
Analgesics
Multidisciplinary
business.industry
Calcium channel
Cortical Spreading Depression
Brain
gabapentinoids
Biological Sciences
medicine.disease
Calcium Channel Blockers
diffusion-weighted MRI
3. Good health
Disease Models
Animal
030104 developmental biology
Diffusion Magnetic Resonance Imaging
Migraine
Cortical spreading depression
Mutation
Systemic administration
business
voltage-gated calcium channel
030217 neurology & neurosurgery
medicine.drug
Zdroj: Proceedings of the National Academy of Sciences, 114(9), 2401-2406
Proceedings of the National Academy of Sciences
Popis: Migraine is characterized by severe headaches that can be preceded by an aura likely caused by cortical spreading depression (SD). The antiepileptic pregabalin (Lyrica) shows clinical promise for migraine therapy, although its efficacy and mechanism of action are unclear. As detected by diffusion-weighted MRI (DW-MRI) in wild-type (WT) mice, the acute systemic administration of pregabalin increased the threshold for SD initiation in vivo. In familial hemiplegic migraine type 1 mutant mice expressing human mutations (R192Q and S218L) in the CaV2.1 (P/Q-type) calcium channel subunit, pregabalin slowed the speed of SD propagation in vivo. Acute systemic administration of pregabalin in vivo also selectively prevented the migration of SD into subcortical striatal and hippocampal regions in the R192Q strain that exhibits a milder phenotype and gain of CaV2.1 channel function. At the cellular level, pregabalin inhibited glutamatergic synaptic transmission differentially in WT, R192Q, and S218L mice. The study describes a DW-MRI analysis method for tracking the progression of SD and provides support and a mechanism of action for pregabalin as a possible effective therapy in the treatment of migraine.
Databáze: OpenAIRE
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