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: Toru Goyagi, Toshiaki Nishikawa, Yoshitsugu Tobe
• Journal: Journal of neurosurgical anesthesiology (J Neurosurg Anesthesiol) Vol. 23 Issue 2 Pg. 131-7 (Apr 2011) ISSN: 1537-1921 [Electronic] United States
• PMID: 21150456 (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

Topics

• 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)