Neuroprotective effects and suppression of ischemia-induced glutamate elevation by β1-adrenoreceptor antagonists administered before transient focal ischemia in rats.

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.
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).
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.
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.
AuthorsToru Goyagi, Toshiaki Nishikawa, Yoshitsugu Tobe
JournalJournal of neurosurgical anesthesiology (J Neurosurg Anesthesiol) Vol. 23 Issue 2 Pg. 131-7 (Apr 2011) ISSN: 1537-1921 [Electronic] United States
PMID21150456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic beta-1 Receptor Antagonists
  • Morpholines
  • Neuroprotective Agents
  • Propanolamines
  • Glutamic Acid
  • landiolol
  • Urea
  • esmolol
  • Norepinephrine
  • Adrenergic beta-1 Receptor Antagonists (pharmacology)
  • Animals
  • Behavior, Animal (drug effects)
  • Blood Gas Analysis
  • Body Temperature (physiology)
  • Brain Chemistry (drug effects)
  • Consciousness Disorders (chemically induced, psychology)
  • Extracellular Space (drug effects, metabolism)
  • Gait Disorders, Neurologic (etiology, psychology)
  • Glutamic Acid (metabolism)
  • Hemodynamics (physiology)
  • Infarction, Middle Cerebral Artery (pathology)
  • Ischemic Attack, Transient (drug therapy, metabolism)
  • Male
  • Microdialysis
  • Morpholines (pharmacology)
  • Neuroprotective Agents
  • Norepinephrine (metabolism)
  • Pain Threshold (drug effects)
  • Propanolamines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reflex (drug effects)
  • Urea (analogs & derivatives, pharmacology)

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