Role of Steroids in Hyperexcitatory Adverse and Anesthetic Effects of Sevoflurane in Neonatal Rats.
Role of Steroids in Hyperexcitatory Adverse and Anesthetic Effects of Sevoflurane in Neonatal Rats.
复制标题
类固醇在新生大鼠七氟醚过度兴奋不良和麻醉作用中的作用
DOI：
10.1159/000437267
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发表时间：
2016
影响因子：
4.1
通讯作者：
Martynyuk AE
中科院分区：
文献类型：
--
作者：
Zhang J;Xu C;Puentes DL;Seubert CN;Gravenstein N;Martynyuk AE
最近的研究表明，新生儿麻醉的长期发育影响在男性中更为突出。我们测试了一般类固醇，特别是性类固醇是否参与了产后早期七氟烷引起的矛盾性皮质癫痫发作的介导。方法：在出生后第 4-6 天，对暴露于 2.1% 七氟烷的雌性 Sprague Dawley 大鼠进行皮层脑电图、海马突触活动、血清类固醇水平和翻正反射 (LORR) 丧失（麻醉效果的标志物）的测量。结果：两性的癫痫发作、脑电图持续峰值和血清皮质酮增加相似。按照效力增强的顺序，皮质类固醇受体拮抗剂 RU 28318、雌二醇受体拮抗剂 ICI 182780 和雌二醇合成抑制剂福美坦可减少七氟醚诱发的癫痫发作。外源性雌二醇会增加七氟烷引起的癫痫发作、峰值和血清皮质酮水平。 ICI 182780 和 NKCC1 抑制剂布美他尼可抑制这些雌二醇增强的癫痫发作和峰值，而 RU 28318 仅减少癫痫发作。在海马 CA1 神经元中，雌二醇增加了 γ-氨基丁酸 A 型受体 (GABAAR) 介导的微型突触后电流的幅度、上升时间和曲线下面积。外源性雌二醇缩短了七氟醚诱导LORR所需的时间，而ICI 182780和福美坦则延长了七氟醚诱导LORR所需的时间。结论：这些发现为七氟醚对该年龄的急性脑电图影响提供了与性别无关的证据。皮质酮和雌二醇参与七氟醚诱发的癫痫发作的介导。雌二醇（而非皮质酮）也通过增强皮质中 GABAAR 介导的兴奋而导致七氟烷引起的峰值。通过增加 GABAAR 介导的大脑更成熟尾部区域的抑制，雌二醇有助于七氟醚诱导的 LORR。
Recent studies have demonstrated that long-term developmental effects of neonatal anesthesia were more prominent in males. We tested whether steroids, in general, and sex steroids, in particular, are involved in the mediation of sevoflurane-caused paradoxical cortical seizures during the early postnatal period. Methods: Cortical electroencephalograms, hippocampal synaptic activity, serum levels of steroids and the loss of the righting reflex (LORR), a marker of anesthetic effect, were measured on postnatal days 4-6 in Sprague Dawley rats of both genders exposed to 2.1% sevoflurane. Results: Episodes of seizures, persistent spikes in electroencephalograms and increases in serum corticosterone were similar in both genders. In the order of increasing potency, the corticosteroid receptor antagonist RU 28318, the estradiol receptor antagonist ICI 182780 and the estradiol synthesis inhibitor formestane decreased sevoflurane-induced seizures. Exogenous estradiol increased sevoflurane-caused seizures, spikes and serum levels of corticosterone. These estradiol-enhanced seizures and spikes were depressed by ICI 182780 and the NKCC1 inhibitor, bumetanide, while RU 28318 decreased seizures only. In hippocampal CA1 neurons, estradiol increased the amplitude, rise time and area under the curve of gamma-aminobutyric acid type A receptor (GABAAR)-mediated miniature postsynaptic currents. Exogenous estradiol shortened, while ICI 182780 and formestane lengthened the time needed for sevoflurane to induce LORR. Conclusion: These findings provide evidence for gender-independent acute electroencephalographic effects of sevoflurane at this age. Corticosterone and estradiol are involved in the mediation of sevoflurane-induced seizures. Estradiol, but not corticosterone, also contributes to sevoflurane-caused spikes, by enhancing GABAAR-mediated excitation in the cortex. By increasing GABAAR-mediated inhibition in more mature caudal regions of the brain, estradiol contributes to sevoflurane-induced LORR.