title: Diffusion-weighted MRI used to detect in vivo modulation of cortical spreading depression: comparison of sumatriptan and tonabersat.
abstract: Spreading cortical depolarization and depression of electroencephalographic activity (SD) may underlie the aura and spreading neurovascular events of migraine. Cortical depolarization may also precipitate the progressive development of cerebral pathology following ischemia. However, data on SD in the human brain are sparse, most likely reflecting the technical difficulties involved in performing such clinical studies. We have previously shown that the transient cerebral water disturbances during SD can be quantitatively investigated in the gyrencephalic brain using repetitive diffusion-weighted magnetic resonance imaging (DWI). To investigate whether DWI could detect modulation of the spatiotemporal properties of SD in vivo, the effects of the antimigraine drug sumatriptan (0.3 mg/kg iv) and the novel anticonvulsant tonabersat (10 mg/kg ip) were evaluated in the cat brain. Supporting previous findings, sumatriptan did not affect the numbers of events (range, 4-8), the duration of SD activity (39.8 +/- 4.4 min, mean +/- SEM), and event velocity (2.2 +/- 0.4 mm min(-1)); tonabersat significantly reduced SD event initiation (range, 0-3) and duration (13.2 +/- 5.0 min) and increased primary event velocity (5.4 +/- 0.7 mm min(-1)). However, both drugs significantly decreased, by >50%, the spatial extent of the first KCl-evoked SD event, and sumatriptan significantly increased event propagation across the suprasylvian sulcus (5.5 +/- 0.6 vs 2.4 +/- 0.4 events in controls). These results demonstrate (1) the feasibility of using DWI to evaluate therapeutic effects on SD, and (2) that sumatriptan may directly modulate the spatial distribution of SD activity in the gyrencephalic brain.
authors.affiliation: Herchel Smith Laboratory for Medicinal Chemistry, University of Cambridge, Robinson Way, Cambridge CB2 2PZ, United Kingdom.
authors.forename: D P
authors.initials: DP
authors.lastname: Bradley
authors.forename: M I
authors.initials: MI
authors.lastname: Smith
authors.forename: C
authors.initials: C
authors.lastname: Netsiri
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: K H
authors.initials: KH
authors.lastname: Bockhorst
authors.forename: L D
authors.initials: LD
authors.lastname: Hall
authors.forename: C L
authors.initials: CL
authors.lastname: Huang
authors.forename: R A
authors.initials: RA
authors.lastname: Leslie
authors.forename: A A
authors.initials: AA
authors.lastname: Parsons
authors.forename: M F
authors.initials: MF
authors.lastname: James
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects* / Q000502:physiology*; D004058:Diffusion; D004569:Electroencephalography; D005240:Feasibility Studies; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011189:Potassium Chloride / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D001549:Benzamides; D001578:Benzopyrans; D017366:Serotonin Receptor Agonists; C118706:tonabersat; D011189:Potassium Chloride; D018170:Sumatriptan