Neuroprotective effects and suppression of ischemia-induced glutamate elevation by β1-adrenoreceptor antagonists administered before transient focal ischemia in rats
| Autor: | Toru Goyagi, Yoshitsugu Tobe, Toshiaki Nishikawa |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Pain Threshold Microdialysis medicine.medical_treatment Morpholines Ischemia Glutamic Acid Pharmacology Neuroprotection Body Temperature Norepinephrine (medication) Propanolamines Rats Sprague-Dawley Norepinephrine Reflex Medicine Animals Urea Saline Gait Disorders Neurologic Brain Chemistry Behavior Animal business.industry Glutamate receptor Hemodynamics Infarction Middle Cerebral Artery Landiolol medicine.disease Esmolol Adrenergic beta-1 Receptor Antagonists Rats Anesthesiology and Pain Medicine Neuroprotective Agents Ischemic Attack Transient Consciousness Disorders Surgery Neurology (clinical) Blood Gas Analysis business Extracellular Space medicine.drug |
| Zdroj: | Journal of neurosurgical anesthesiology. 23(2) |
| ISSN: | 1537-1921 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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