Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia.
Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia.
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DOI：
10.1097/aln.0000000000003883
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发表时间：
2021-10-01
期刊：
影响因子：
8.8
通讯作者：
Nehs CJ
中科院分区：
文献类型：
--
作者：
Melonakos ED;Siegmann MJ;Rey C;O'Brien C;Nikolaeva KK;Solt K;Nehs CJ
臂旁核兴奋可降低与增强γ - 氨基丁酸A型受体作用的麻醉剂相关的皮质δ波振荡（0.5 - 4Hz）功率和恢复时间。臂旁核兴奋对具有其他分子靶点的麻醉剂（如右美托咪定和氯胺酮）的影响尚不清楚。我们假设臂旁核兴奋会在右美托咪定和氯胺酮麻醉期间引起觉醒。
利用仅由设计药物激活的设计受体（DREADDs），我们在成年雄性大鼠（无麻醉，9只大鼠）、使用右美托咪定（低剂量：0.3μg·kg⁻¹·min⁻¹，持续45分钟，8只大鼠；高剂量：4.5μg·kg⁻¹·min⁻¹，持续10分钟，7只大鼠）或氯胺酮（低剂量：2mg·kg⁻¹·min⁻¹，持续30分钟，7只大鼠；高剂量：4mg·kg⁻¹·min⁻¹，持续15分钟，8只大鼠）的情况下，兴奋臂旁核区域的钙/钙调蛋白依赖性蛋白激酶2α阳性神经元。在对照实验（相同大鼠和处理）中，我们不兴奋DREADDs。我们记录并分析脑电图和麻醉恢复时间。
在150分钟的分析期间内，除了两个短暂时间段外，臂旁核兴奋在使用低剂量右美托咪定时降低了额叶脑电图中的δ波功率（右美托咪定输注期间氯氮平 - N - 氧化物 - 生理盐水的峰值中位数自举差异 = - 6.06[99%置信区间：- 12.36至 - 1.48]dB，P = 0.007）。然而，臂旁核兴奋在使用高剂量右美托咪定以及低剂量和高剂量氯胺酮时降低δ波功率的效果较差（高剂量[右美托咪定、氯胺酮]输注期间的峰值中位数自举差异 = [ - 1.93， - 0.87]dB，99%置信区间 = [ - 4.16至 - 0.56， - 1.62至 - 0.18]dB，P = [0.006，0.019]；低剂量氯胺酮在输注期间无统计学显著降低）。臂旁核兴奋引起的恢复时间差异在右美托咪定（[低、高]剂量的中位数差异 = [1.63，11.01]分钟，95%置信区间 = [ - 20.06至14.14， - 20.84至23.67]分钟，P = [0.945，0.297]）和低剂量氯胺酮（中位数差异 = 12.82[95%置信区间： - 3.20至39.58]分钟，P = 0.109）中无统计学显著性，但在高剂量氯胺酮中显著更长（中位数差异 = 11.38[95%置信区间：1.81至24.67]分钟，P = 0.016）。
这些结果表明，臂旁核兴奋改变麻醉的神经生理和行为效应的有效性取决于麻醉剂的分子靶点。
Parabrachial nucleus excitation reduces cortical delta oscillation (0.5–4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric-acid-type-A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. We hypothesized that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. Using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we excited calcium/calmodulin-dependent protein kinase 2 alpha-positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (9 rats), with dexmedetomidine (low-dose: 0.3 μg·kg−1·min−1 for 45 mins, 8 rats; high-dose: 4.5 μg·kg−1·min−1 for 10 mins, 7 rats), or with ketamine (low-dose: 2 mg·kg−1·min−1 for 30 mins, 7 rats; high-dose: 4 mg·kg−1·min−1 for 15 mins, 8 rats). For control experiments (same rats and treatments), we did not excite DREADDs. We recorded and analyzed the electroencephalogram and anesthesia recovery time. Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-minute analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide – saline] during dexmedetomidine infusion = −6.06 [99% CIs: −12.36 to −1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [−1.93, −0.87] dB, 99% CIs = [−4.16 to −0.56, −1.62 to −0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] mins, 95% CIs = [−20.06 to 14.14, −20.84 to 23.67] mins, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CIs: −3.20 to 39.58] mins, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CIs: 1.81 to 24.67] mins, P = 0.016). These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic’s molecular target.