Bumetanide Alleviates Epileptogenic and Neurotoxic Effects of Sevoflurane in Neonatal Rat Brain

被引:153
作者
Edwards, David A. [1 ]
Shah, Hina P. [1 ]
Cao, Wengang [1 ]
Gravenstein, Nikolaus [1 ]
Seubert, Christoph N. [1 ]
Martynyuk, Anatoly E. [1 ]
机构
[1] Univ Florida, Dept Anesthesiol, JHMHC, Gainesville, FL 32610 USA
关键词
GAMMA-AMINOBUTYRIC-ACID; CL-COTRANSPORTER KCC2; ELECTROCONVULSIVE-THERAPY; IMMATURE NEURONS; GABA RESPONSES; CELL-DEATH; SEIZURES; ANESTHESIA; EMERGENCE; PROPOFOL;
D O I
10.1097/ALN.0b013e3181cf9138
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: We tested the hypothesis that in newborn rats, sevoflurane may cause seizures, neurotoxicity, and impairment in synaptic plasticity-effects that may be diminished by the Na+-K+-2Cl(-) cotransporter 1 inhibitor, bumetanide. Methods: Electroencephalography, activated caspase-3, and hippocampal long-term potentiation were measured in rats exposed to 2.1% sevoflurane for 0.5-6 h at postnatal days 4-17 (P4-P17). Results: Arterial blood gas samples drawn at a sevoflurane concentration of 2.1% showed no evidence of either hypoxia or hypoventilation in spontaneously breathing rats. Higher doses of sevoflurane (e.g., 2.9%) caused respiratory depression. During anesthesia maintenance, the electroencephalography exhibited distinctive episodes of epileptic seizures in 40% of P4-P8 rats. Such seizure-like activity was not detected during anesthesia maintenance in P10-P17 rats. Emergence from 3 h of anesthesia with sevoflurane resulted in tonic/clonic seizures in some P10-P17 rats but not in P4-P8 rats. Bumetanide (5 mu mol/kg, intraperitoneally) significantly decreased seizures in P4-P9 rats but did not affect the emergence seizures in P10-P17 rats. Anesthesia of P4 rats with sevoflurane for 6 h caused a significant increase in activated caspase-3 and impairment of long-term potentiation induction measured at 1 and 14-17 days after exposure to sevoflurane, respectively. Pretreatment of P4 rats with bumetanide nearly abolished the increase in activated caspase-3 but did not alleviate impairment of long-term potentiation. Conclusion: These results support the possibility that excitatory output of sevoflurane-potentiated gamma-aminobutyric acid type A/glycine systems may contribute to epileptogenic and neurotoxic effects in early postnatal rats.
引用
收藏
页码:567 / 575
页数:9
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