Inhibitory effect of MS-153 on elevated brain glutamate level induced by rat middle cerebral artery occlusion.

Abstract

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-beta-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.

• Authors: K Umemura, T Gemba, A Mizuno, M Nakashima
• Journal: Stroke (Stroke) Vol. 27 Issue 9 Pg. 1624-8 (Sep 1996) ISSN: 0039-2499 [Print] United States
• PMID: 8784139 (Publication Type: Journal Article)

Chemical References

• 5-methyl-1-nicotinoyl-2-pyrazoline
• Nicotinic Acids
• Glutamine
• Glutamic Acid
• Glycine

Topics

• Animals
• Arterial Occlusive Diseases (metabolism, pathology)
• Brain (drug effects, metabolism)
• Cerebral Arteries
• Cerebral Infarction (pathology)
• Glutamic Acid (metabolism)
• Glutamine (metabolism)
• Glycine (metabolism)
• Male
• Nicotinic Acids (pharmacology)
• Osmolar Concentration
• Rats
• Rats, Wistar