Manzella Francesca M, Gulvezan Bethany F, Maksimovic Stefan, Useinovic Nemanja, Raol Yogendra H, Joksimovic Srdjan M, Jevtovic-Todorovic Vesna, Todorovic Slobodan M
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Front Behav Neurosci. 2021 Nov 1;15:703859. doi: 10.3389/fnbeh.2021.703859. eCollection 2021.
General anesthetics are neurotoxic to the developing rodent and primate brains leading to neurocognitive and socio-affective impairment later in life. In addition, sleep patterns are important predictors of cognitive outcomes. Yet, little is known about how anesthetics affect sleep-wake behaviors and their corresponding oscillations. Here we examine how neonatal general anesthesia affects sleep and wake behavior and associated neuronal oscillations. We exposed male and female rat pups to either 6 h of continuous isoflurane or sham anesthesia (compressed air) at the peak of their brain development (postnatal day 7). One cohort of animals was used to examine neurotoxic insult 2 h post-anesthesia exposure. At weaning age, a second cohort of rats was implanted with cortical electroencephalogram electrodes and allowed to recover. During adolescence, we measured sleep architecture (divided into wake, non-rapid eye movement, and rapid eye movement sleep) and electroencephalogram power spectra over a 24 h period. We found that exposure to neonatal isoflurane caused extensive neurotoxicity but did not disrupt sleep architecture in adolescent rats. However, these animals had a small but significant reduction in beta oscillations, specifically in the 12-20 Hz beta 1 range, associated with wake behavior. Furthermore, beta oscillations play a critical role in cortical development, cognitive processing, and homeostatic sleep drive. We speculate that dysregulation of beta oscillations may be implicated in cognitive and socio-affective outcomes associated with neonatal anesthesia.
全身麻醉药对发育中的啮齿动物和灵长类动物大脑具有神经毒性,会导致其日后出现神经认知和社会情感障碍。此外,睡眠模式是认知结果的重要预测指标。然而,关于麻醉药如何影响睡眠-觉醒行为及其相应的脑电振荡,人们知之甚少。在此,我们研究新生儿全身麻醉如何影响睡眠和觉醒行为以及相关的神经元振荡。我们在雄性和雌性幼鼠大脑发育的高峰期(出生后第7天),让它们持续接受6小时的异氟烷麻醉或假麻醉(压缩空气)。一组动物在麻醉暴露后2小时用于检查神经毒性损伤。在断奶期,将另一组大鼠植入皮质脑电图电极并使其恢复。在青春期,我们在24小时内测量了睡眠结构(分为觉醒、非快速眼动睡眠和快速眼动睡眠)和脑电图功率谱。我们发现,新生儿期暴露于异氟烷会导致广泛的神经毒性,但不会破坏青春期大鼠的睡眠结构。然而,这些动物与觉醒行为相关的β振荡,特别是在12-20赫兹的β1范围内,出现了轻微但显著的减少。此外,β振荡在皮质发育、认知加工和稳态睡眠驱动中起着关键作用。我们推测,β振荡的失调可能与新生儿麻醉相关的认知和社会情感结果有关。