title: The competitive NMDA antagonist, CGS-19755, improves postischemic hypoperfusion in selectively vulnerable regions in gerbils.
abstract: We attempted to clarify the effects of an NMDA antagonist on postischemic hypoperfusion in gerbils with 10 min forebrain ischemia and to relate it to postischemic metabolic recovery. We administered 10 mg/kg of CGS-19755, a competitive NMDA antagonist, or the same volume of saline intraperitoneally 30 min before the vascular occlusion. In 26 gerbils, we measured local cerebral blood flow (LCBF) 60 min after the reperfusion using [14C]iodoantipyrine autoradiography. In 20 gerbils, the effects on metabolic recovery were determined by serial measurements of intracellular pH, adenosine triphosphate (ATP) and the ratio between phosphocreatine and inorganic phosphate (PCr/Pi) until 60 min after reperfusion using 31P-magnetic resonance spectroscopy. In another group of 24 gerbils, we determined histopathological damage 24 h after the ischemia. The LCBF autoradiograms in the control group consistently demonstrated a typical postischemic hypoperfusion, i.e. homogeneous 50-75% reduction of blood flow in all forebrain structures. In contrast, CGS-19755 pretreatment animals showed highly heterogeneous LCBF declines, and significantly higher LCBF values were observed in the frontoparietal cortex and thalamus both of which were the most vulnerable area in this model. No significant LCBF change was observed in sham operated animals with or without CGS-19755 pretreatment. The postischemic recovery of PCr/Pi in gerbils pretreated with CGS-19755 was significantly better than that in the control animals. No significant differences in the recovery of ATP and intracellular pH were observed. The histological damage in the CGS-19755-treated group was less extensive than those in the saline-treated group. CGS-19755 pretreatment improved postischemic hypoperfusion and PCr/Pi recovery in the 10-min forebrain ischemia model in gerbils. The improvement of postischemic hypoperfusion in selectively vulnerable regions suggests that the activation of NMDA receptors may be related to the mechanism of developing postischemic hypoperfusion.
authors.affiliation: Department of Medicine, National Cardiovascular Center, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Omae
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: J
authors.initials: J
authors.lastname: Ogata
authors.forename: K
authors.initials: K
authors.lastname: Tamaki
authors.forename: K
authors.initials: K
authors.lastname: Minematsu
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009474:Neurons / Q000469:parasitology; D010758:Phosphorus; D010875:Pipecolic Acids / Q000627:therapeutic use*; D016548:Prosencephalon / Q000098:blood supply* / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D010758:Phosphorus; C053672:selfotel