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(Stroke. 1996;27:1624-1628.)
© 1996 American Heart Association, Inc.

Articles

Inhibitory Effect of MS-153 on Elevated Brain Glutamate Level Induced by Rat Middle Cerebral Artery Occlusion

Kazuo Umemura, MD, PhD; Takefumi Gemba, PhD; Atsuhiro Mizuno, PhD Mitsuyoshi Nakashima, MD, PhD

the Department of Pharmacology, Hamamatsu University School of Medicine (Japan).

Correspondence to Dr K. Umemura, Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-cho Hamamatsu, 431-31 Japan. E-mail umemura@hama-med.ac.jp.

Background and Purpose In this study we investigated the effects of a novel compound, MS-153 ([R]-[-]-5-methyl-1-nicotinoyl-2-pyrazoline), on elevated brain glutamate concentrations and cerebral infarct volume induced by middle cerebral artery (MCA) occlusion in the rat.

Methods The rat MCA was occluded by a thrombus induced by a photochemical reaction between green light and the photosensitizer dye rose bengal, which causes endothelial injury followed by formation of a platelet- and fibrin-rich thrombus at the site of photochemical reaction; this method is routinely used in our laboratory to produce arterial occlusion in experimental animals. Extracellular glutamate concentration at the ischemic border zone was determined by a microdialysis technique. The size of cerebral infarction was measured by a histochemical technique 24 hours after MCA occlusion. MS-153 was administered at various doses as a continuous infusion for 24 hours, beginning 0 to 2 hours after MCA occlusion.

Results At the ischemic border zone, the concentration of glutamate in the extracellular fluid increased by 40-fold after ischemia. At 3.13 mg/kg per hour, MS-153 reduced glutamate concentration (P<.05) and also the size of ischemic cerebral infarction (P<.05). Furthermore, the glutamate uptake inhibitor DL-threo-ß-hydroxyaspartate reversed the effect of MS-153 on glutamate concentration.

Conclusions The reduction in the size of cerebral infarction by MS-153 may be attributable to the inhibition of glutamate release or an increase in cellular glutamate uptake.

Editorial Comment

Kevin G Peters, MD, Guest Editor

Duke University Medical Center, Durham, NC

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