Evidence for a role of the N-methyl-d-aspartate (NMDA) receptor in cortical spreading depression in the rat

Marrannes, Roger; Willems, Roland; Prins, E. De; Wauquier, A.

doi:10.1016/0006-8993(88)90690-7

Cited by 305 publications

(186 citation statements)

References 45 publications

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“…The GABA A receptor is now accepted as a common target for many general anesthetics (Campagna, et al, 2003, Garrett and Gan, 1998, Hara and Harris, 2002, but enhanced GABAergic transmission is unlikely to modulate CSD susceptibility since barbiturates do not suppress CSD (Brand, et al, 1998, Kitahara, et al, 2001, Van Harreveld and Stamm, 1953. Relevant for CSD suppression, however, are the NMDA subtype of glutamate receptors, inhibition of which potently reduces CSD speed and duration, and blocks CSD (Gorelova, et al, 1987, Hernandez-Caceres, et al, 1987, Marrannes, et al, 1988, Obrenovitch and Zilkha, 1996. Interaction with NMDA receptors has thus far been convincingly demonstrated for isoflurane and N 2 O. Isoflurane causes modest inhibition of NMDA receptors, likely via the noncompetitive glycine site (Carla and Moroni, 1992, Dickinson, et al, 2007, Solt, et al, 2006.…”

Section: Discussionmentioning

confidence: 99%

The impact of anesthetics and hyperoxia on cortical spreading depression

Kudo

Nozari

Moskowitz

et al. 2008

Experimental Neurology

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Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura. It negatively impacts tissue injury during stroke, cerebral contusion and intracranial hemorrhage. Susceptibility to CSD has been assessed in several experimental animal models in vivo, such as after topical KCl application or cathodal stimulation. Various combinations of anesthetics and ambient conditions have been used by different laboratories making comparisons problematic and differences in data difficult to reconcile. We systematically studied CSD susceptibility comparing commonly used experimental anesthetics (isoflurane, α-chloralose, urethane) with or without N 2 O or normobaric hyperoxia (100% O 2 inhalation). The frequency of evoked CSDs, and their propagation speed, duration, and amplitude were recorded during 2 hour topical KCl (1M) application. We found that N 2 O reduced CSD frequency when combined with isoflurane or urethane, but not α-chloralose; N 2 O also decreased CSD propagation speed and duration. Urethane anesthesia was associated with the highest CSD frequency that was comparable to pentobarbital. Inhalation of 100% O 2 did not alter CSD frequency, propagation speed or duration in combination with any of the anesthetics tested. Our data show anesthetic modulation of CSD susceptibility in an experimental model of human disease, underscoring the importance of proper study design for hypothesis testing as well as for comparing results between studies.

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Section: Discussionmentioning

confidence: 99%

The impact of anesthetics and hyperoxia on cortical spreading depression

Kudo

Nozari

Moskowitz

et al. 2008

Experimental Neurology

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“…Depolar ization presumably spreads by release of glutamate, as evidenced by its blockade with glutamate antag onists (Marrannes et al, 1988). Glutamate is widely held to be a mediator of ischemic cell injury because the resulting cytosolic calcium flooding is thought to cause irreversible damage (Siesj6 and Bengtsson, 1989).…”

Section: Discussionmentioning

confidence: 99%

Cortical Negative DC Deflections following Middle Cerebral Artery Occlusion and KCl-Induced Spreading Depression: Effect on Blood Flow, Tissue Oxygenation, and Electroencephalogram

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Kohno

Hossmann

1994

J Cereb Blood Flow Metab

286

130

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Summary: In the periphery of ischemic brain lesions, transient spreading depression-like direct current (DC) deflections occur that may be of pathophysiological im portance for determining the volume of the ischemic in farct. The effect of these deflections on cerebral blood flow, tissue oxygen tension, and electrophysiology was studied in rats submitted to intraluminal thread occlusion of the middle cerebral artery (MCA) and compared with the changes following potassium chloride (KCl)-induced spreading depression of intact animals, Immediately after MCA occlusion, cortical laser-Doppler flow (LDF) in the periphery of the MCA territory sharply decreased to 35 ± 14% of control (mean ± SD; p < 0,05), tissue P02 de clined from 28 ± 4 to 21 ± 3 mm Hg (p < 0.05), and EEG power fell to -80% of control. During 7-h occlusion, 3-11 DC deflections with a mean duration of 5.2 ± 4.8 min occurred at irregular intervals, and EEG power gradually During the last years, several laboratories have been able to show that glutamate antagonists reduce the volume of ischemic infarcts (Ozyurt et aI. , 1988; Park et aI., 1988; Dirnagl et aI., 1990). The thera peutical effect could not be attributed to increased cerebral blood flow (Park et aI., 1989; Iijima et aI., 1992), indicating that molecular mechanisms are in volved. This observation is widely held to support an excitotoxic mechanism of brain infarcts in anal ogy to glutamate toxicity in vitro (Choi, 1985) and the phenomenon of delayed neuronal death in se lectively vulnerable brain regions following a period of global ischemia (Suzuki et aI., 1983). The com-

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“…54 Similar inhibitory effects on CSD initiation, propagation, and duration were produced in vivo by NMDA antagonists in a dose-dependent manner. 55 Moreover, a decrease in intracortical glutamate was measured by in vivo microdialysis during high K ϩ exposure in leaner and tottering mice. 54 Thus, Ca V 2.1-dependent release of glutamate from cortical excitatory synapses appears crucial in determining both initiation and propagation of CSD.…”

Section: Familial Hemiplegic Migraine Type 1 (Fhm1)mentioning

confidence: 99%

Familial Hemiplegic Migraine

2007

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Summary: Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A and SCNA1A, encoding the pore-forming ␣ 1 subunits of the neuronal voltage-gated Ca 2ϩ channels Ca V 2.1 and Na ϩ channels Na V 1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the ␣ 2 subunit of the Na ϩ , K ϩ adenosinetriphosphatase (ATPase), are responsible for FHM2. This review discusses the functional studies of two FHM1 knockin mice and of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1 FHM3). These studies show the following: (1) FHM1 mutations produce gain-of-function of the Ca V 2.1 channel and, as a consequence, increased Ca V 2.1-dependent neurotransmitter release from cortical neurons and facilitation of in vivo induction and propagation of cortical spreading depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations produce loss-of-function of the ␣ 2 Na ϩ ,K ϩ -ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na V 1.5 (and presumably Na V 1.1) channels. These findings are consistent with the hypothesis that FHM mutations share the ability of rendering the brain more susceptible to CSD by causing either excessive synaptic glutamate release (FHM1) or decreased removal of K ϩ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K ϩ (FHM3). The FHM data support a key role of CSD in migraine pathogenesis and point to cortical hyperexcitability as the basis for vulnerability to CSD and to migraine attacks. Hence, they support novel therapeutic strategies that consider CSD and cortical hyperexcitability as key targets for preventive migraine treatment.

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Evidence for a role of the N-methyl-d-aspartate (NMDA) receptor in cortical spreading depression in the rat

Cited by 305 publications

References 45 publications

The impact of anesthetics and hyperoxia on cortical spreading depression

The impact of anesthetics and hyperoxia on cortical spreading depression

Cortical Negative DC Deflections following Middle Cerebral Artery Occlusion and KCl-Induced Spreading Depression: Effect on Blood Flow, Tissue Oxygenation, and Electroencephalogram

Familial Hemiplegic Migraine

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