| Project/Area Number |
17591609
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Akita University |
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Principal Investigator |
GOYAGI Toru Akita University, School of Medicine, Lecturer (30302277)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Toshiaki Akita University, School of Medicine, Professor (50156048)
KIMURA Testu Akita University, School of Medicine, Assistant Professor (00312702)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | β-adrenorecentor antagonists / esmolol / landiolol / neuronrotective effects / middle cerebral artery occlusion / βブロッカー / グルタミン酸 |
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| Research Abstract |
Introduction: β-adrenoreceptor antagonists experimentally reduce cardiac and renal injury following ischemia, and also are clinically useful for myocardial infarction and severe burn. In addition, β-adrenoreceptor antagonists have neuroprotective effects in focal cerebral ischemia in experimental settings. The present study was conducted to evaluate the neuroprotective effects of selective β-adrenoreceptor antagonists transient focal cerebral ischemia.
Methods: Halothane anesthetized normothermic adult male Sprague-Dawley rats were subjected to 2 hr of middle cerebral artery occlusion (MCAO) using the intraluminal suture technique confirmed by laser Doppler flowmetry. 1) Rats received intravenous infusion of saline 0.5 ml/hr, esmolol 200 μ g/kg/min, or landiolol 50 μ g/kg/min. Infusion was initiated 30 min prior to MCAO and continued for 24 hr. The brains were removed and stained with triphenyltetrazolium chloride (TTC) at 7 days after reperfusion. 2) Before MCAO, the microdialysis prob
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e was stereotactically placed into the striatum. Glutamate in the striatum was measured during MCAO and reperfusion. 3) The brain was harvested and stained by TUNEL assay at 4 days after reperfusion. 4) Infusion was initiated 30 min after MCAO and continued for 24 hr. 7 days after reperfusion, the brains were removed and stained. 5) Other rats were received 10 times dose of experiment 1 and allowed to survive for 7 days.
Results: 1) Neurological deficit scores were smaller in the rats treated with esmolol, and landiolol, compared to control rats at 1 day, as well as at 4 days, and 7 days. The infarct volumes of cortical and striatum were less in the rats receiving (β-adrenoreceptor antagonists than in saline-treated rats. 2) The area under the curve of Glutamate of the striatum in the saline treated rat was significantly less than that in the esmolol-and landiolol-treated rat. 3) The numbers of TUNEL positive cells in the saline treated rats were greater than 4) The infarct volumes of cortical. And striatum were less in the rats receiving β-adrenoreceptor antagonists than in saline-treated rats. 5) The infarct volumes of cortical and striatum were less in the rats receiving β-adrenoreceptor antagonists than in saline-treated rats, whereas there were no differences between normal and 10 times dose in esmolol-and landiolol-treated rat.
Conclusion: The current study indicates that the administration of selective β1-adrenoreceptor antagonists improve neurological and histological outcomes following transient focal cerebral ischemia in rats even post treatment with β1 antagonists after MCAO. One of the mechanisms of these neuroprotection is due to suppress the glutamate concentration and apotosis. Less
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