title: Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI.
abstract: Cortical spreading depression (CSD) is a phenomenon implicated in migraine with aura and associated with other neurological disorders (e.g. stroke, brain trauma). Current evidence points to the essential role of NMDA receptors in CSD mechanisms. However, the roles of multiple subunits of NMDA receptors expressed in neurons, glia and blood vessels in vivo, are little explored. Using BOLD fMRI of urethane anesthetized rats as an integrative CSD readout, we tested the involvement of different NMDA receptor subtypes in CSD induction and propagation. Rats were treated with a non-selective NMDA blocker (MK-801), NR2B antagonist (ifenprodil) or a NR2A selective antagonist (TCN-201). CSD was induced during fMRI scanning by application of KCl onto the cerebral cortex and fMRI data were collected by 9.4 T MRI. The non-specific NMDA antagonist MK-801 completely blocked CSD, which was not observed in the NR2A group where TCN-201 did not alter the CSD features. Unexpectedly, the NR2B specific antagonist ifenprodil largely promoted the initial negative phase of the BOLD CSD response, likely due to altered neurovascular coupling. Our data suggest key roles and differential involvement of NMDA receptor subtypes in CSD generation and propagation, highlighting an important role for the NR2B subtype.
authors: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio 70700, Finland. Electronic address: artem.shatillo@uef.fi.
authors: Artem
authors: A
authors: Shatillo
authors: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio 70700, Finland. Electronic address: raimo.salo@uef.fi.
authors: Raimo A
authors: RA
authors: Salo
authors: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio 70700, Finland; Lab of Neurobiology, Kazan Federal University, 18 Kremlyovskaya St., Kazan 420008, Republic of Tatarstan, Russian Federation. Electronic address: rashid.giniatullin@uef.fi.
authors: Rashid
authors: R
authors: Giniatullin
authors: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio 70700, Finland. Electronic address: olli.grohn@uef.fi.
authors: Olli H
authors: OH
authors: Gröhn
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D011189:Potassium Chloride; D010100:Oxygen
keywords: BOLD; Dizocilpine, MK-801 (PubChem CID: 180081); Glutamate; Ifenprodil (PubChem CID: 11957579); NMDA receptors; Spreading depression; TCN-201 (PubChem CID: 4787937); fMRI