Bumetanide, an Inhibitor of NKCC1 (Na-K-2Cl Cotransporter Isoform 1), Enhances Propofol-Induced Loss of Righting Reflex but Not Its Immobilizing Actions in Neonatal Rats

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Oct 27

PMID 27783647

Citations 4

Authors

Yukihide Koyama

Tomio Andoh

Yoshinori Kamiya

Tomoyuki Miyazaki

Koichi Maruyama

Takayuki Kariya

Takahisa Goto

Affiliations

Soon will be listed here.

Abstract

Gamma-aminobutyric acid (GABA) has been shown to induce excitation on immature neurons due to increased expression of Na+-K+-2Cl- co-transporter isoform 1 (NKCC1), and the transition of GABAergic signaling from excitatory to inhibitory occurs before birth in the rat spinal cord and spreads rostrally according to the developmental changes in cation-chloride co-transporter expression. We previously showed that midazolam activates the hippocampal CA3 area and induces less sedation in neonatal rats compared with adolescent rats in an NKCC1-dependent manner. In the present study, we tested the hypothesis that propofol-induced loss of righting reflex (LORR) but not immobilizing actions are modulated by NKCC1-dependent mechanisms and reduced in neonatal rats compared with adolescent rats. We estimated neuronal activity in the cortex, hippocampus and thalamus after propofol administration with or without bumetanide, an NKCC1 inhibitor, by immunostaining of phosphorylated cyclic adenosine monophosphate-response element binding protein (pCREB). We studied effects of bumetanide on propofol-induced LORR and immobilizing actions in postnatal day 7 and 28 (P7 and P28) rats. The pCREB expression in the cortex (P = 0.001) and hippocampus (P = 0.01) was significantly greater in the rats receiving propofol only than in the rats receiving propofol plus bumetanide at P 7. Propofol-induced LORR or immobilizing effects did not differ significantly between P7 and P28. Bumetanide significantly enhanced propofol-induced LORR (P = 0.031) but not immobilization in P7 rats. These results are partially consistent with our hypothesis. They suggest that propofol may activate the rostral but not caudal central nervous system dependently on NKCC1, and these differential actions may underlie the different properties of sedative and immobilizing actions observed in neonatal rats.

Citing Articles

Development of NMDA receptors contributes to the enhancement of electroencephalogram oscillations under volatile anesthetics in rats.

Zhang M, Chen Y, Liu J, Yang Y, Wang R, Zhang D Front Neural Circuits. 2023; 16:1065374.

PMID: 36589861 PMC: 9797678. DOI: 10.3389/fncir.2022.1065374.

Extracellular Hydraulic Resistance Enhances Cell Migration.

Maity D, Bera K, Li Y, Ge Z, Ni Q, Konstantopoulos K Adv Sci (Weinh). 2022; 9(29):e2200927.

PMID: 36031406 PMC: 9561764. DOI: 10.1002/advs.202200927.

CLP290 promotes the sedative effects of midazolam in neonatal rats in a KCC2-dependent manner: A laboratory study in rats.

Doi A, Miyazaki T, Mihara T, Ikeda M, Niikura R, Andoh T PLoS One. 2021; 16(3):e0248113.

PMID: 33711029 PMC: 7954344. DOI: 10.1371/journal.pone.0248113.

Blast-Induced Traumatic Brain Injury Triggered by Moderate Intensity Shock Wave Using a Modified Experimental Model of Injury in Mice.

Zhou Y, Wen L, Wang H, Zhou X, Fang J, Zhu J Chin Med J (Engl). 2018; 131(20):2447-2460.

PMID: 30334530 PMC: 6202591. DOI: 10.4103/0366-6999.243558.

References

Wang S, Zhang X, Song C, Xiao T, Zhao M, Zhu G . In vivo effects of bumetanide at brain concentrations incompatible with NKCC1 inhibition on newborn DGC structure and spontaneous EEG seizures following hypoxia-induced neonatal seizures. Neuroscience. 2014; 286:203-15. DOI: 10.1016/j.neuroscience.2014.11.031. View

Baker R, Gent T, Yang Q, Parker S, Vyssotski A, Wisden W . Altered activity in the central medial thalamus precedes changes in the neocortex during transitions into both sleep and propofol anesthesia. J Neurosci. 2014; 34(40):13326-35. PMC: 4180471. DOI: 10.1523/JNEUROSCI.1519-14.2014. View

Scher M, Alvin J, Gaus L, Minnigh B, Painter M . Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use. Pediatr Neurol. 2003; 28(4):277-80. DOI: 10.1016/s0887-8994(02)00621-5. View

Jugovac I, Imas O, Hudetz A . Supraspinal anesthesia: behavioral and electroencephalographic effects of intracerebroventricularly infused pentobarbital, propofol, fentanyl, and midazolam. Anesthesiology. 2006; 105(4):764-78. DOI: 10.1097/00000542-200610000-00023. View

Musienko P, Zelenin P, Lyalka V, Orlovsky G, Deliagina T . Postural performance in decerebrated rabbit. Behav Brain Res. 2008; 190(1):124-34. PMC: 2365477. DOI: 10.1016/j.bbr.2008.02.011. View

Hyde T, Lipska B, Ali T, Mathew S, Law A, Metitiri O . Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. J Neurosci. 2011; 31(30):11088-95. PMC: 3758549. DOI: 10.1523/JNEUROSCI.1234-11.2011. View

Kaila K, Price T, Payne J, Puskarjov M, Voipio J . Cation-chloride cotransporters in neuronal development, plasticity and disease. Nat Rev Neurosci. 2014; 15(10):637-54. PMC: 4294553. DOI: 10.1038/nrn3819. View

Ma J, Shen B, Stewart L, Herrick I, Leung L . The septohippocampal system participates in general anesthesia. J Neurosci. 2002; 22(2):RC200. PMC: 6758657. View

Ben-Ari Y, Gaiarsa J, Tyzio R, Khazipov R . GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev. 2007; 87(4):1215-84. DOI: 10.1152/physrev.00017.2006. View

10.

Yu D, Jiang Y, Gao J, Liu B, Chen P . Repeated exposure to propofol potentiates neuroapoptosis and long-term behavioral deficits in neonatal rats. Neurosci Lett. 2013; 534:41-6. DOI: 10.1016/j.neulet.2012.12.033. View

11.

Koyama R, Tao K, Sasaki T, Ichikawa J, Miyamoto D, Muramatsu R . GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy. Nat Med. 2012; 18(8):1271-8. DOI: 10.1038/nm.2850. View

12.

Puskarjov M, Kahle K, Ruusuvuori E, Kaila K . Pharmacotherapeutic targeting of cation-chloride cotransporters in neonatal seizures. Epilepsia. 2014; 55(6):806-18. PMC: 4284054. DOI: 10.1111/epi.12620. View

13.

Kubo K, Nishikawa K, Hardy-Yamada M, Ishizeki J, Yanagawa Y, Saito S . Altered responses to propofol, but not ketamine, in mice deficient in the 65-kilodalton isoform of glutamate decarboxylase. J Pharmacol Exp Ther. 2009; 329(2):592-9. DOI: 10.1124/jpet.109.151456. View

14.

Kungys G, Kim J, Jinks S, Atherley R, Antognini J . Propofol produces immobility via action in the ventral horn of the spinal cord by a GABAergic mechanism. Anesth Analg. 2009; 108(5):1531-7. PMC: 3148181. DOI: 10.1213/ane.0b013e31819d9308. View

15.

Glykys J, Dzhala V, Kuchibhotla K, Feng G, Kuner T, Augustine G . Differences in cortical versus subcortical GABAergic signaling: a candidate mechanism of electroclinical uncoupling of neonatal seizures. Neuron. 2009; 63(5):657-72. PMC: 2932871. DOI: 10.1016/j.neuron.2009.08.022. View

16.

Cacheaux L, Topf N, Tibbs G, Schaefer U, Levi R, Harrison N . Impairment of hyperpolarization-activated, cyclic nucleotide-gated channel function by the intravenous general anesthetic propofol. J Pharmacol Exp Ther. 2005; 315(2):517-25. DOI: 10.1124/jpet.105.091801. View

17.

Tao X, Finkbeiner S, Arnold D, Shaywitz A, Greenberg M . Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron. 1998; 20(4):709-26. DOI: 10.1016/s0896-6273(00)81010-7. View

18.

Andrada J, Livingston P, Lee B, Antognini J . Propofol and etomidate depress cortical, thalamic, and reticular formation neurons during anesthetic-induced unconsciousness. Anesth Analg. 2011; 114(3):661-9. DOI: 10.1213/ANE.0b013e3182405228. View

19.

Koch S, Fitzgerald M, Hathway G . Midazolam potentiates nociceptive behavior, sensitizes cutaneous reflexes, and is devoid of sedative action in neonatal rats. Anesthesiology. 2007; 108(1):122-9. DOI: 10.1097/01.anes.0000296079.45446.15. View

20.

Bovill J, Sonner J, Zhang Y, Stabernack C, Abaigar W, Xing Y . GABA(A) receptor blockade antagonizes the immobilizing action of propofol but not ketamine or isoflurane in a dose-related manner. Anesth Analg. 2003; 96(3):706-712. DOI: 10.1213/01.ANE.0000048821.23225.3A. View