Glutamate Receptor Antagonists in Experimental Focal Cerebral Ischaemia

McCulloch, James; Özyurt, Emin; Park, C K; Nehls, Daniel G.; Teasdale, Graham M.; Graham, David I.

doi:10.1007/978-3-7091-9266-5_11

Cited by 27 publications

(27 citation statements)

References 22 publications

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“…(1994) and Gill et a!. (1995) and confirms the well-documented fact that glutamate antagonists amelio rate ischemic brain damage (McCulloch, 1994).…”

Section: Discussionsupporting

confidence: 54%

Potassium-Induced Cortical Spreading Depressions during Focal Cerebral Ischemia in Rats: Contribution to Lesion Growth Assessed by Diffusion-Weighted NMR and Biochemical Imaging

Busch

Gyngell

Eis

et al. 1996

J Cereb Blood Flow Metab

257

164

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Summary: In focal ischemia of rats, the volume of ischemic lesion correlates with the number of peri-infarct depolariza tions, To test the hypothesis that depolarizations accelerate in farct growth, we combined focal ischemia with externally evoked spreading depression (SD) waves, Ischemic brain in farcts were produced in halothane-anaesthetized rats by intra luminal thread occlusion of the middle cerebral artery (MCA), In one group of animals, repeated SDs were evoked at IS-min intervals by microinjections of potassium acetate into the fron tal cortex, In another group, the spread of the potassium-evoked depolarizations was prevented by application of the N-methyl D-aspartate (NMDA) receptor antagonist dizocilpine (MK-80 I), The volume of ischemic lesion was monitored for 2 h by diffusion-weighted imaging (DWI) and correlated with electro physiological recordings and biochemical imaging techniques, In untreated rats, each microinjection produced an SD wave and a stepwise rise of the volume and signal intensity of the In focal cerebral ischemia of rat infarct size correlates with the number of peri-infarct spreading depression (SD)-like depolarizations (Mies et aI., 1993; Chen et aI., 1993). These depolarizations are generated in the border zone of the ischemic lesion and spread into the peri infarct surrounding (Nedergaard and Hansen, 1993; Ne dergaard and Astrup, 1986). Glutamate antagonists such as dizocilpine (MK-801) or 2,3-dihydroxy-6-nitro-7-Received January I L 1996; final received May 3. 1996; accepted May 29, 1996.Address correspondence. and reprint requests to Prof. Dr. K.-A. Hossmann, Max-Planck-Institut fUr neurologische Forschung. Gleuelerstrasse 50, D-50931 Kiiln, FR Germany.Abbreviations used: ADC, apparent diffusion coefficient; ANOY A. analysis of variance; DC, direct current; DWl, diffusion-weighted im aging; MCA, middle carotid artery; MR, magnetic resonance; NBQX, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F)-quinoxaline; NMDA, N methyl-D-aspartate; RF, radiofrequency; ROI, region of interest; SD, spreading depression; TE. spin echo. 1090DWI-visible cortical lesion, The volume of this lesion in creased between IS min and 2 h of MCA occlusion from 19 ± 15% to 66 ± 16% of ipsilateral cortex, In dizocilpine-treated animals, microinjections of potassium did not evoke SDs, nor did the volume and signal intensity of the DWI-visible cortical lesion change, At 15 min after MCA occlusion, the DWI visible lesion was larger than in untreated animals-43 ± 16% of the ipsilateral cortex; however, after 2 h, it increased only slightly further to 49 ± 21 %. Slower lesion growth in the ab sence of SDs was also reflected by the volume of ATP-depleted tissue, which, after 2 h of MCA occlusion, involved 26 ± 12% of the ipsilateral cortex in treated and 49 ± 9% in untreated animals (p < 0.(1). These observations support the hypothesis that peri-infarct depolarizations accelerate cerebral infarct growth.

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“…(1994) and Gill et a!. (1995) and confirms the well-documented fact that glutamate antagonists amelio rate ischemic brain damage (McCulloch, 1994).…”

Section: Discussionsupporting

confidence: 54%

Potassium-Induced Cortical Spreading Depressions during Focal Cerebral Ischemia in Rats: Contribution to Lesion Growth Assessed by Diffusion-Weighted NMR and Biochemical Imaging

Busch

Gyngell

Eis

et al. 1996

J Cereb Blood Flow Metab

257

164

View full text Add to dashboard Cite

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“…At first, NMDA antagonists were considered as having great potential as neuroprotective agents (McCulloch 1994), but most clinical trials have been disappointing as the drugs caused psychomimetic and cardiovascular side effects severely limiting their usefulness (Menniti et al 2000). Nevertheless, specific subunit-selective NMDA antagonists may still preserve neuroprotective properties without causing significant side effects (Menniti et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Ifenprodil Against Spreading Depression in the Mouse Entorhinal Cortex

Faria¹,

Módy²

2004

Journal of Neurophysiology

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Faria, Leonardo Coutinho and Istvan Mody. Protective effect of ifenprodil against spreading depression in the mouse entorhinal cortex. J Neurophysiol 92: 2610 -2614, 2004. First published June 16, 2004 10.1152/jn.00466.2004. In the brain, spreading depression (SD) is characterized by a large extracellular DC shift, a massive failure of ion homeostasis and a transient cessation of neuronal function. Clinically, SD is believed to be involved in various neurological disorders including migraine and cerebrovascular diseases. The propagation of cortical SD requires the release of glutamate, and N-methyl-D-aspartate (NMDA) receptors play a crucial role in this process. Here, we have isolated the NMDA receptor-mediated component of extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) in layers 2-3 of the entorhinal cortex of murine brain slices. In the absence of GABA A and AMPA receptor-mediated synaptic transmission, stimulation of layer 6 afferents every 15-90 s elicited spontaneous SD on average within 18.5 min after the start of the stimulation. In the presence of ifenprodil, an NR2B receptor subunit-selective NMDA receptor antagonist, the occurrence of SD was nearly abolished. Our results are consistent with an important role of NR2B subunits in triggering SD in the entorhinal cortex.

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“…(ϩ)-5-Methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801) is a potent noncompetitive NMDA receptor antagonist widely used to block glutamateinduced death in a spectrum of in vitro neuronal models, and myriad examples attest to its effectiveness in attenuating ischemic damage in animals (Gill et al, 1992;McCulloch et al, 1993). However, long-term inactivation of NMDA receptor function by MK-801 is lethal to cortical neurons (Hwang et al, 1999), suggesting that a shorter, more controlled MK-801 exposure could possibly evoke a pharmacologically induced preconditioning of cortical cells.…”

Section: Abstract: Apoptosis; Death Signals; Lethal Injury; Mk-801; mentioning

confidence: 99%

Transient NMDA Receptor Inactivation Provides Long-Term Protection to Cultured Cortical Neurons from a Variety of Death Signals

et al. 2000

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NMDA receptor antagonists, such as (ϩ)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801), potently block glutamate-induced neuronal death in myriad in vitro cell models and effectively attenuate ischemic damage in vivo. In this report, a novel role for MK-801 and other NMDA receptor antagonists in preconditioning neurons to withstand a wide range of subsequent lethal insults is described. A brief 30 min exposure to 0.1 M MK-801, applied up to 96 hr before a "lethal" insult, protected primary cortical neurons from a diverse group of neurotoxic agents, including NMDA, ␤-amyloid, staurosporine, etoposide, and oxygen-glucose deprivation. This neuroprotective preconditioning by MK-801 arose from transient NMDA receptor inactivation, because the noncompetitive NMDA receptor antagonists memantine and nylindin and the competitive antagonist AP-5 gave similar effects. MK-801 protection was dependent on new protein synthesis during the first 2 hr, but not from 2 to 5 hr, after MK-801 exposure. The MK-801 transient did not alter the ability of NMDA to trigger normally lethal [Ca 2ϩ ] i influx 48 hr later, but it did block early downstream signaling events coupled to NMDA neurotoxicity, including PKC inactivation and the activation of calpain. Moreover, MK-801 protected neurons from staurosporine-induced apoptosis, although caspase activation in these cells was unimpeded. It is likely that the stress associated with transient inactivation of NMDA receptors triggered a rapid compensatory survival response that provided long-term protection from a spectrum of insults, inducing apoptotic and nonapoptotic death. The possibility that MK-801 preconditioning blocks an event common to seemingly diverse death mechanisms suggests it will be an important tool for obtaining a clearer understanding of the salient molecular events at work in neuronal death and survival pathways.

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Glutamate Receptor Antagonists in Experimental Focal Cerebral Ischaemia

Cited by 27 publications

References 22 publications

Potassium-Induced Cortical Spreading Depressions during Focal Cerebral Ischemia in Rats: Contribution to Lesion Growth Assessed by Diffusion-Weighted NMR and Biochemical Imaging

Potassium-Induced Cortical Spreading Depressions during Focal Cerebral Ischemia in Rats: Contribution to Lesion Growth Assessed by Diffusion-Weighted NMR and Biochemical Imaging

Protective Effect of Ifenprodil Against Spreading Depression in the Mouse Entorhinal Cortex

Transient NMDA Receptor Inactivation Provides Long-Term Protection to Cultured Cortical Neurons from a Variety of Death Signals

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