Neuroprotective Effect of YM9OK, an AMPA-Receptor Antagonist,against Delayed Neuronal Death Induced by Transient Global Cerebral Ischemia in Gerbils and Rats.

Kawasaki-Yatsugi, Sachiko; Yatsugi, Shin-ichi; Koshiya, Kazuo; Shimizu‐Sasamata, Masao

doi:10.1254/jjp.74.253

Cited by 30 publications

(6 citation statements)

References 26 publications

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“…Experimental studies bolster the idea that neuronal excitotoxicity can involve the activation of AMPA‐ and KA‐type glutamate receptors (Chen et al, 1995; Nakai et al, 2000; Moldrich et al, 2000; Hermann et al, 2001). The AMPA/KA receptor antagonist 6‐nitro‐7‐sulfamoyl‐(f)‐quinoxaline‐2, 3‐dione (NBQX) and some of its derivatives have shown protective effects against CNS damage induced by either transient global ischemia (Buchan et al, 1991; Diemer et al, 1992; Sheardown et al, 1993; Kawasaki‐Yatsugi et al, 1997; Turski et al, 1998; O'Neill et al, 2000) or traumatic injury (Wrathall et al, 1997; Rosenberg et al, 1999). Previous studies have also described the effect of KA on neurons in culture (Cox et al, 1990; Kato et al, 1991; Resink et al, 1994; Fryer et al, 1999; Ha et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Kainate induces rapid redistribution of the actin cytoskeleton in ameboid microglia

Christensen

Sun

et al. 2006

J of Neuroscience Research

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Microglia are key mediators of the immune response in the central nervous system (CNS). They are closely related to macrophages and undergo dramatic morphological and functional changes after CNS trauma or excitotoxic lesions. Microglia can be directly stimulated by excitatory neurotransmitters and are known to express many neurotransmitter receptors. The role of these receptors, however, is not clear. This study describes the microglial response to the glutamate receptor agonist kainate (KA) and shows via immunochemistry that the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptor subunit GluR1 is present on cultured microglia. In the presence of 100 microM or 1 mM KA, cultured microglia underwent dramatic morphological and cytoskeletal changes as observed by time-lapse photography and quantitative confocal analysis of phalloidin labeling. KA-stimulated microglia showed condensation of cytoplasmic actin filaments, rapid de- and repolymerization, and cytoplasmic redistribution of condensed actin bundles. Rearrangement of actin filaments-thought to be involved in locomotion and phagocytosis and to indicate an increased level of activation (for reviews see Greenberg [ 1995] Trends Cell Biol. 5:93-99; Imai and Kohsaka [ 2002] Glia 40:164-174)-was significantly increased in treated vs. control cultures. Morphological plasticity and membrane ruffling were also seen. These findings suggest direct microglial excitation via glutamate receptor pathways. Thus, neurotransmitter release after brain or spinal cord injury might directly modulate the inflammatory response.

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Section: Discussionmentioning

confidence: 99%

Kainate induces rapid redistribution of the actin cytoskeleton in ameboid microglia

Christensen

Sun

et al. 2006

J of Neuroscience Research

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“…The inhibitory effect of theanine on the AMPA receptor is 10-fold higher than its inhibitory effect on the NMDA receptor. AMPA receptor antagonists provide protection against ischemia induced by middle cerebral artery (MCA) occlusion in rats (Xue et al, 1994;Umemura et al, 1997;Kawasaki-Yatsugi et al, 1998) and forebrain ischemia in gerbils and rats (Sheardown et al, 1993;Kawasaki-Yatsugi et al, 1997). It was previously reported that twice-repeated ischemia, but not single ischemia, impaired spatial memory in rats and caused neuronal cell death characterized by an increase in the number of apoptotic cells in the hippocampal CA1 field (Iwasaki et al, 2004).…”

Section: Animalsmentioning

confidence: 99%

Theanine prevents memory impairment induced by repeated cerebral ischemia in rats

Egashira

Ishigami

et al. 2007

Phytotherapy Research

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The present study investigated the neuroprotective effect of γ γ γ γ γ-glutamylethylamide (theanine), a component Japanese green tea (Camellia sinensis), on memory impairment induced by twice-repeated cerebral ischemia in rats. Theanine was injected i.p. immediately after the first occlusion. Theanine (0.3 and 1 mg/kg) significantly prevented the impairment of spatial memory in rats subjected to repeated cerebral ischemia, 7 days after the second reperfusion. Moreover, theanine (1 mg/kg) significantly inhibited the decrease in the number of surviving cells in the hippocampal CA1 field in the same rats. These results suggest that theanine prevents memory impairment induced by repeated cerebral ischemia, in part by protecting against neuronal cell death, and that it might be useful for preventing cerebrovascular disease.

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“…Global cerebral ischaemia causes delayed neuronal loss leading to impaired learning and memory. Both the quinoxaline and 2,3‐benzodiazepine type AMPA antagonists rescued a large fraction of pyramidal cells in the CA1 area of the hippocampus after BCO in the gerbil and after four‐vessel occlusion (4VO) in the rat (Kawasaki‐Yatsugi et al , 1997; Gyertyán et al , 1999; Nielsen et al , 1999; Kapus et al , 2004). Non‐competitive AMPA antagonists decreased hypermotility and increased spontaneous alternation response, a measure of spatial memory, after global cerebral ischaemia in gerbils (Gyertyán et al , 1999; Kapus et al , 2004).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective and anticonvulsant effects of EGIS‐8332, a non‐competitive AMPA receptor antagonist, in a range of animal models

Gigler

Móricz

Ágoston

et al. 2007

British J Pharmacology

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Background and purpose: Blockade of AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors is a good treatment option for a variety of central nervous system disorders. The present study evaluated the neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, as a potential drug candidate. Experimental approach: AMPA antagonist effects of EGIS-8332 were measured using patch-clamp techniques. Neuroprotective and anticonvulsant effects of EGIS-8332 were evaluated in various experimental models, relative to those of GYKI 53405. Key results: EGIS-8332 inhibited AMPA currents in rat cerebellar Purkinje cells and inhibited the AMPA-and quisqualateinduced excitotoxicity in primary cultures of telencephalon neurons (IC 50 ¼ 5.1-9.0 mM), in vitro. Good anticonvulsant actions were obtained in maximal electroshock-, sound-and chemically-induced seizures (range of ED 50 ¼ 1.4-14.0 mg kg À1 i.p.) in mice. Four days after transient global cerebral ischaemia, EGIS-8332 decreased neuronal loss in the hippocampal CA1 area in gerbils and rats. EGIS-8332 dose-dependently reduced cerebral infarct size after permanent middle cerebral artery occlusion in mice and rats (minimum effective dose ¼ 3 mg kg À1 i.p.). Side effects of EGIS-8332 emerged much above its pharmacologically active doses. A tendency for better efficacy of GYKI 53405 than that of EGIS-8332 was observed in anticonvulsant tests that reached statistical significance in few cases, while the contrary was perceived in cerebral ischaemia tests. Conclusions and implications: EGIS-8332 seems suitable for further development for the treatment of epilepsy, ischaemia and stroke based on its efficacy in a variety of experimental disease models, and on its low side effect potential.

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Neuroprotective Effect of YM9OK, an AMPA-Receptor Antagonist,against Delayed Neuronal Death Induced by Transient Global Cerebral Ischemia in Gerbils and Rats.

Abstract: ABSTRACT-We investigated the neuroprotective effect of the ƒ¿-amino-3-hydroxy-5-methylisoxazole-4

Cited by 30 publications

References 26 publications

Kainate induces rapid redistribution of the actin cytoskeleton in ameboid microglia

Kainate induces rapid redistribution of the actin cytoskeleton in ameboid microglia

Theanine prevents memory impairment induced by repeated cerebral ischemia in rats

Neuroprotective and anticonvulsant effects of EGIS‐8332, a non‐competitive AMPA receptor antagonist, in a range of animal models

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