Neuroprotective Effects of Remifentanil Against Transient Focal Cerebral Ischemia in Rats
| Autor: | Seongheon Lee, Seok Jai Kim, Jong-Un Lee, Seongtae Jeong, Cheol-Won Jeong, Hyejin Jeong, Kyung Yeon Yoo |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
MAPK/ERK pathway medicine.drug_class Narcotic Antagonists p38 mitogen-activated protein kinases Blotting Western Remifentanil Ischemia Blood Pressure Pharmacology Neuroprotection Rats Sprague-Dawley Brain ischemia Piperidines Naltrindole Animals Medicine Dose-Response Relationship Drug Interleukin-6 Tumor Necrosis Factor-alpha business.industry Infarction Middle Cerebral Artery Carbon Dioxide medicine.disease Receptor antagonist Naltrexone Rats Neuroprotective Agents Anesthesiology and Pain Medicine Ischemic Attack Transient Reperfusion Injury Anesthesia Surgery Neurology (clinical) Mitogen-Activated Protein Kinases Nervous System Diseases business Anesthetics Intravenous medicine.drug |
| Zdroj: | Journal of Neurosurgical Anesthesiology. 24:51-57 |
| ISSN: | 0898-4921 |
| DOI: | 10.1097/ana.0b013e3182368d70 |
| Popis: | Background Opioid agonists have been implicated in neuroprotection from hypoxic injury through regulating mitogen-activated protein kinases and cytokines. We determined the effects of remifentanil in focal brain ischemia and reperfusion (I/R) injury. Mechanisms linked to mitogen-activated protein kinases, including extracellular signaling-regulated kinase (ERK) 1/2, p38 kinases, and c-Jun N-terminal kinase (JNK), and various cytokines were also examined. Methods Male Sprague-Dawley rats were subjected to an I/R insult consisting of 90 minutes' middle cerebral artery occlusion (MCAO) followed by reperfusion under general anesthesia. Neurological deficit scores and infarct volume were determined after 24 hours of reperfusion. Remifentanil (5 μg/kg/min) was given alone or combined with naltrindole (δ-opioid receptor antagonist; 1 mg/kg), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (μ-opioid receptor antagonist; 1 mg/kg), or 5'-guanidinonaltrindole (κ-opioid receptor antagonist; 1 mg/kg). Opioid antagonists were administered 20 minutes before MCAO. Remifentanil infusion was started 10 minutes before MCAO and continued throughout. The control group was without drugs. The expression levels of ERK1/2, p38, and JNK, and also those of tumor necrosis factor-α (TNF-α) and interleukin-6, were determined after 1, 3, and 24 hours of reperfusion. Results Remifentanil significantly improved the functional outcome and reduced the infarct volumes (69.0±24.3 mm(3) vs. 108.9±24.8 mm(3)), which were not affected by D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) or 5'-guanidinonaltrindole, but were abolished by naltrindole. The I/R insult enhanced the phosphorylation of ERK 1/2 and the expression of TNF-α, which were significantly reduced by remifentanil. Neither the phosphorylation of p38 and JNK nor the production of interleukin-6 was altered throughout the experiment. Conclusions Remifentanil may be neuroprotective against focal I/R injury, possibly through the activation of δ-opioid receptors and attenuation of ERK 1/2 activity and TNF-α production, in the rat brain. |
| Databáze: | OpenAIRE |
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