title: Neuroprotective effects and suppression of ischemia-induced glutamate elevation by β1-adrenoreceptor antagonists administered before transient focal ischemia in rats.
abstract: BACKGROUND
  β-Adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. This study was conducted to compare the neuroprotective effects of low-dose and high-dose of selective β1-adrenoreceptor antagonists in rats after focal cerebral ischemia. We also investigated whether glutamate and norepinephrine contribute to neuroprotection of the β-adrenoreceptor antagonists.
  
  
  METHODS
  Sprague-Dawley rats were subjected to 120 minutes middle cerebral artery occlusion. The rats received intravenous infusion of saline 0.5 mL/h, esmolol 200, esmolol 2000, landiolol 50, or landiolol 500 μg/kg/min. Infusion of all the drugs were started 30 minutes before ischemia and continued for 24 hours. Neurological deficit scores were evaluated at 1, 4, and 7 days, whereas the brains were removed and stained at 7 days after ischemia. In the esmolol 200, and landiolol 50 μg/kg/min groups of additional rats, glutamate and norepinephrine concentrations in the striatum were measured separately by microdialysis during ischemia (glutamate, 120 min; norepinephrine, 110 min) and reperfusion (40 min).
  
  
  RESULTS
  Neurological deficit scores were smaller in rats treated with esmolol or landiolol than in saline-treated rats at 1, 4, and 7 days. The cortical and striatal infarct volumes were smaller in rats receiving β-adrenoreceptor antagonists than in the saline-treated rats. There were no significant differences in neurological score or infarct volume between the groups receiving the different doses of β1-adrenoreceptor antagonists. The area under the curve of glutamate in the esmolol-treated or landiolol-treated rats was significantly smaller than that in the saline-treated rats, whereas no significant differences were noted in the norepinephrine concentration among the groups.
  
  
  CONCLUSIONS
  This study indicates that the improvement in neurological and histologic outcomes by selective β1-adrenoreceptor antagonists after transient focal cerebral ischemia is partly attributed to attenuation of glutamate release.
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Akita, Japan. tgoyagi@doc.med.akita-u.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Goyagi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Tobe
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D003244:Consciousness Disorders / Q000139:chemically induced / Q000523:psychology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000523:psychology; D018698:Glutamic Acid / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents; D009638:Norepinephrine / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D009025:Morpholines; D018696:Neuroprotective Agents; D011412:Propanolamines; D018698:Glutamic Acid; C077049:landiolol; D014508:Urea; C036604:esmolol; D009638:Norepinephrine