• Toru Goyagi, Toshiaki Nishikawa, and Yoshitsugu Tobe.
• Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Akita, Japan. tgoyagi@doc.med.akita-u.ac.jp
• J Neurosurg Anesthesiol. 2011 Apr 1;23(2):131-7.

Backgroundβ-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.MethodsSprague-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).ResultsNeurological 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.ConclusionsThis 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.

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