The Effect of the α2-Agonist Dexmedetomidine and the N-Methyl-d-Aspartate Antagonist S(+)-Ketamine on the Expression of Apoptosis-Regulating Proteins After Incomplete Cerebral Ischemia and Reperfusion in Rats
- 1 February 2003
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Anesthesia & Analgesia
- Vol. 96 (2), 524-531
- https://doi.org/10.1213/00000539-200302000-00041
Abstract
In this study, we investigated whether the neuroprotection previously seen with dexmedetomidine or S(+)-ketamine involves regulation of proapoptotic (Bax and p53) and antiapoptotic (Bcl-2 and Mdm-2) proteins. Rats were anesthetized with isoflurane. After surgical preparation of isoflurane was discontinued, animals were randomly assigned to receive fentanyl and nitrous oxide (N2O)/oxygen plus 100 μg/kg of dexmedetomidine intraperitoneally 30 min before ischemia (n = 8), 1 mg · kg−1 · min−1 of S(+)-ketamine and oxygen/air (n = 8), or fentanyl and N2O/oxygen (n = 8; control group). In all three treatment groups, incomplete cerebral ischemia (30 min) was induced by unilateral carotid artery occlusion and hemorrhagic hypotension to a mean arterial blood pressure of 30–35 mm Hg. Four hours after the start of reperfusion, the brains were removed, and the expression of apoptosis-regulating proteins was determined by using immunofluorescence and Western blot analysis. The results were compared with sham-operated animals (n = 8). After cerebral ischemia/reperfusion, the relative protein concentration of Bax was increased by 110% in control animals compared with the dexmedetomidine- and S(+)-ketamine-treated rats and by 140% compared with the sham-operated animals. In animals treated with dexmedetomidine, the expression of Bcl-2 and Mdm-2 was larger compared with control (68% and 210%, respectively) or sham-operated (110% and 180%, respectively) animals. Therefore, it is possible that the neuroprotective properties of dexmedetomidine and S(+)-ketamine seen in previous studies involve ultra-early modulation of the balance between pro- and antiapoptotic proteins.This publication has 23 references indexed in Scilit:
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