Propofol-induced electroencephalographic seizures in neonatal rats: the role of corticosteroids and γ-aminobutyric acid type A receptor-mediated excitation.
Propofol-induced electroencephalographic seizures in neonatal rats: the role of corticosteroids and γ-aminobutyric acid type A receptor-mediated excitation.
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DOI：
10.1213/ane.0000000000000529
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发表时间：
2015-02
影响因子：
5.7
通讯作者：
Martynyuk A
中科院分区：
文献类型：
--
作者：
Willis J;Zhu W;Perez-Downes J;Tan S;Xu C;Seubert C;Gravenstein N;Martynyuk A
发育中的中枢神经系统兴奋和抑制之间的不平衡可能导致病理生理学结果。我们研究了内分泌活动和γ-氨基丁酸A型受体（GABAAR）介导的兴奋在新生大鼠GABAAR选择性麻醉剂丙泊酚引起的脑电图癫痫发作中的机制作用。出生后第4-6天的Sprague道利大鼠在腹腔内给予丙泊酚（40 mg kg-1）之前和之后1小时进行小手术，植入电极以测量脑电图活动。在丙泊酚给药前15 min给予各种治疗。异丙酚麻醉期间出现癫痫发作和持续性低振幅棘波。在接受与用于研究脑电活动相同的实验操作的动物中，异丙酚给药后1小时，检测到血清皮质酮（t（10）=-5.062; P= 0.0005）和醛固酮（t（10）=-5.069; P= 0.0005）水平成倍增加。布美他尼（Na+-K+-2Cl-共转运体抑制剂）预处理可减少GABAAR介导的兴奋，消除丙泊酚引起的癫痫发作和棘波脑电图活动。盐皮质激素和糖皮质激素受体拮抗剂RU 28318和RU 486可抑制脑电图癫痫发作，但不影响丙泊酚的棘波脑电图效应。足以引起翻正反射丧失的剂量的依托咪酯在增加血清皮质类固醇水平和诱发脑电癫痫发作方面作用较弱。给皮质酮预处理的大鼠幼仔给予依托咪酯进一步延长了外源性皮质酮给药引起的脑电图癫痫发作的总持续时间（t（21）=-2.512，P = 0.0203）。丙泊酚增加新生大鼠全身皮质类固醇水平，这沿着GABAAR介导的兴奋似乎是丙泊酚诱导的新生儿脑电图癫痫发作所必需的。单独增强GABAAR活性可能不足以引起新生儿脑电图癫痫发作。
An imbalance between excitation and inhibition in the developing central nervous system may result in a pathophysiological outcome. We investigated he mechanistic roles of endocrine activity and gamma-aminobutyric acid type A receptor (GABAAR)-mediated excitation in electroencephalographic seizures caused by the GABAAR-selective anesthetic propofol in neonatal rats. Postnatal day 4–6 Sprague Dawley rats underwent a minor surgical procedure to implant electrodes to measure electroencephalographic activity for 1 h before and 1 h after intraperitoneal administration of propofol (40 mg kg−1). Various treatments were administered 15 min before administration of propofol. Episodes of electroencephalographic seizures and persistent low-amplitude spikes occurred during propofol anesthesia. Multifold increases in serum levels of corticosterone (t(10) = −5.062; P= 0.0005) and aldosterone (t(10) = −5.069; P= 0.0005) were detected 1 h after propofol administration in animals that underwent experimental manipulations identical to those used to study electroencephalographic activity. Pretreatment with bumetanide, the Na+–K+–2Cl– co-transporter inhibitor, which diminishes GABAAR-mediated excitation, eliminated both seizure and spike electroencephalographic activities caused by propofol. Mineralocorticoid and glucocorticoid receptor antagonists, RU 28318 and RU486, depressed electroencephalographic seizures but did not affect the spike electroencephalographic effects of propofol. Etomidate, at a dose sufficient to induce loss of righting reflex, was weak at increasing serum corticosteroid levels and eliciting electroencephalographic seizures. Etomidate given to corticosterone-pretreated rat pups further increased the total duration of electroencephalographic seizures caused by administration of exogenous corticosterone (t(21) = −2.512, P = 0.0203). Propofol increases systemic corticosteroid levels in neonatal rats, which along with GABAAR-mediated excitation appear to be required for propofol-induced neonatal electroencephalographic seizures. Enhancement of GABAAR activity alone may not be sufficient to elicit neonatal electroencephalographic seizures.