GABAA受体效应与新生儿癫癎治疗
The Effect of GABAA Receptor and Its Treatment of Neonatal Epilepsy
DOI: 10.12677/ACM.2019.98142, PDF,   
作者: 肖 潇, 王曼丽, 汤继宏：苏州大学附属儿童医院，江苏 苏州
关键词: 新生儿癫癎；GABAA受体；治疗；NKCC1；Neonatal Epilepsy； GABAA Receptor； Treatment； NKCC1
摘要: 近年来的研究显示苯巴比妥类等针对性作用于GABAA受体的药物在新生儿癫癎治疗中的临床疗效不佳，且可能导致进一步的远期脑损害，原因在于新生脑中GABAA受体表现为兴奋性效应，随着神经系统发育而逐渐转化为成熟脑中的重要抑制性受体。位于神经元细胞膜上的转运蛋白NKCC1、KCC2及L型Ca2+通道共同参与了新生期GABAA受体激活后兴奋性效应的形成。
Abstract: The drug phenobarbital which acts as GABAA receptor modulator is recently found to have a poor clinical outcome and even a long-term injury to brain. The reason may lie on the excitatory effect of GABAA receptor in developing brain rather than the inhibitory effect in developed brain. Trans-porter NKCC1 and KCC2 along with L-type Ca2+ channel take part in the generation of the excitatory effect, which indicates a new way of target therapy of neonatal epilepsy.
文章引用：肖潇, 王曼丽, 汤继宏. GABAA受体效应与新生儿癫癎治疗[J]. 临床医学进展, 2019, 9(8): 926-930. https://doi.org/10.12677/ACM.2019.98142

参考文献

[1] Staley, K. (2015) Molecular Mechanisms of Epilepsy. Nature Neuroscience, 18, 367. [Google Scholar] [CrossRef] [PubMed]
[2] Dang, L.T. and Silverstein, F.S. (2017) Drug Treatment of Seizures and Ep-ilepsy in Newborns and Children. Pediatric Clinics of North America, 64, 1291-1308. [Google Scholar] [CrossRef] [PubMed]
[3] Bell, G.S., Neligan, A. and Sander, J.W. (2014) An Unknown Quantity—The Worldwide Prevalence of Epilepsy. Epilepsia, 55, 958-962. [Google Scholar] [CrossRef] [PubMed]
[4] Vento, M., de Vries, L.S., Alberola, A., et al. (2009) Approach to Seizures in the Neonatal Period: A European Perspective. Acta Paediatrica, 99, 497-501. [Google Scholar] [CrossRef] [PubMed]
[5] Vezzani, A., Aronica, E., Mazarati, A. and Pittman, Q.J. (2013) Epilepsy and Brain Inflammation. Experimental Neurology, 244, 11-21. [Google Scholar] [CrossRef] [PubMed]
[6] Nardou, R., Ferrari, D.C. and Ben-Ari, Y. (2013) Mecha-nisms and Effects of Seizures in the Immature Brain. Seminars in Fetal & Neonatal Medicine, 18, 175-184. [Google Scholar] [CrossRef] [PubMed]
[7] Miller, S.M., Goasdoue, K. and Björkman, S.T. (2017) Neonatal Seizures and Disruption to Neurotransmitter Systems. Neural Regeneration Research, 12, 216-217. [Google Scholar] [CrossRef] [PubMed]
[8] Dupuis, N. and Auvin, S. (2015) Inflammation and Epilepsy in the Developing Brain: Clinical and Experimental Evidence. CNS Neuroscience & Therapeutics, 21, 141-151. [Google Scholar] [CrossRef] [PubMed]
[9] Whitehead, E., Dodds, L., Joseph, K.S., et al. (2006) Relation of Pregnancy and Neonatal Factors to Subsequent Development of Childhood Epilepsy: A Population-Based Cohort Study. Pediatrics, 117, 1298-1306. [Google Scholar] [CrossRef] [PubMed]
[10] Jembrek, M.J. and Vlainic, J. (2015) GABA Receptors: Pharmaco-logical Potential and Pitfalls. Current Pharmaceutical Design, 21, 4943-4959. [Google Scholar] [CrossRef] [PubMed]
[11] Chuang, S.H. and Reddy, D.S. (2018) Genetic and Molecular Regulation of Extrasynaptic GABA-A Receptors in the Brain: Therapeutic Insights for Epilepsy. Journal of Pharmacology and Experimental Therapeutics, 364, 180-197. [Google Scholar] [CrossRef] [PubMed]
[12] World Health Organization (2013) Standard Antiepileptic Drugs (Phenobarbital, Pheny-Toin, Carbamazepine, Valproic Acid) for Management of Convulsive Epilepsy in Adults and Children in WHO Mental Health Gap Action Programme mhGAP, mhGAP Evidence Resource Center, Epilepsy and Seizures. WHO, Geneva.
[13] Glykys, J. and Staley, K.J. (2015) Diazepam Effect during Early Neonatal Development Correlates with Neuronal Cl-. Annals of Clinical and Translational Neurology, 2, 1055-1070. [Google Scholar] [CrossRef] [PubMed]
[14] Vesoulis, Z.A. and Mathur, A.M. (2014) Advances in Management of Ne-onatal Seizures. Indian Journal of Pediatrics, 81, 592-598. [Google Scholar] [CrossRef] [PubMed]
[15] Sands, T.T. and Mcdonough, T.L. (2016) Recent Advances in Neonatal Seizures. Current Neurology and Neuroscience Reports, 16, 92. [Google Scholar] [CrossRef] [PubMed]
[16] Ikonomidou, C. (2009) Triggers of Apoptosis in the Immature Brain. Brain & Development, 31, 488-492. [Google Scholar] [CrossRef] [PubMed]
[17] Kirmse, K., Witte, O.W. and Holthoff, K. (2011) GABAergic Depolarization during Early Cortical Development and Implications for Anticonvulsive Therapy in Neonates. Epilepsia, 52, 1532-1543. [Google Scholar] [CrossRef] [PubMed]
[18] Wang, D.D. and Kriegstein, A.R. (2011) Blocking Early GABA Depolarization with Bumetanide Results in Permanent Alterations in Cortical Circuits and Sensorimotor Gating Deficits. Cerebral Cortex, 21, 574-587. [Google Scholar] [CrossRef] [PubMed]
[19] Chamma, I., Chevy, Q., Poncer, J.C., et al. (2012) Role of the Neuronal K-Cl Co-Transporter KCC2 in Inhibitory and Excitatory Neurotransmission. Frontiers in Cellular Neuroscience, 6, 5. [Google Scholar] [CrossRef] [PubMed]
[20] Kirmse, K., Witte, O.W. and Holthoff, K. (2010) GABA Depolarizes Immature Neocortical Neurons in the Presence of the Ketone Body β-Hydroxybutyrate. Journal of Neuroscience, 30, 16002-16007. [Google Scholar] [CrossRef] 
[21] Holmes, G.L. (2009) The Long-Term Effects of Neonatal Seizures. Clinics in Perinatology, 36, 901-904. [Google Scholar] [CrossRef] [PubMed]
[22] Kalkman, H.O. (2011) Alterations in the Expression of Neuronal Chloride Transporters May Contribute to Schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psy-chiatry, 35, 410-414. [Google Scholar] [CrossRef] [PubMed]
[23] Hernan, A.E. and Holmes, G.L. (2016) Antiepileptic Drug Treatment Strategies in Neonatal Epilepsy. Progress in Brain Research, 226, 179-193. [Google Scholar] [CrossRef] [PubMed]
[24] Yamada, J., Okabe, A., Toyoda, H., Kilb, W., Luhmann, H.J. and Fukuda, A. (2004) Cl− Uptake Promoting Depolarizing GABA Actions in Immature Rat Neocortical Neurones Is Me-diated by NKCC1. The Journal of Physiology, 557, 829-841. [Google Scholar] [CrossRef] [PubMed]
[25] Succol, F., Fiumelli, H., Benfenati, F., et al. (2012) Intracellular Chloride Concentration Influences the GABAA Receptor Subunit Composition. Nature Communications, 3, 738. [Google Scholar] [CrossRef] [PubMed]
[26] Tyzio, R., Nardou, R., Ferrari, D.C., et al. (2014) Oxytocin-Mediated GABA Inhibition during Delivery Attenuates Autism Pathogenesis in Rodent Offspring. Science, 343, 675-679. [Google Scholar] [CrossRef] [PubMed]
[27] Sipila, S.T., Huttu, K., Yamada, J., et al. (2009) Compensatory En-hancement of Intrinsic Spiking upon NKCC1 Disruption in Neonatal Hippocampus. Journal of Neuroscience, 29, 6982-6988. [Google Scholar] [CrossRef] 
[28] Wang, D.D. and Kriegstein, A.R. (2008) GABA Regu-lates Excitatory Synapse Formation in the Neocortex via NMDA Receptor Activation. Journal of Neuroscience, 28, 5547-5558. [Google Scholar] [CrossRef] 
[29] Kahle, K.T., Barnett, S.M., Sassower, K.C., et al. (2009) Decreased Seizure Activity in a Human Neonate Treated with Bumetanide, an Inhibitor of the NAt-Kt-2Cle Cotransporter NKCC1. Journal of Child Neurology, 24, 572e6. [Google Scholar] [CrossRef] [PubMed]
[30] Cleary, R.T., Sun, H., Huynh, T., et al. (2013) Bumetanide En-hances Phenobarbital Efficacy in a Rat Model of Hypoxic Neonatal Seizures., PLoS ONE, 8, e57148. [Google Scholar] [CrossRef] [PubMed]
[31] Löscher, W., Puskarjov, M. and Kaila, K. (2013) Cation-Chloride Cotransporters NKCC1 and KCC2 as Potential Targets for Novel Antiepileptic and Antiepileptogenic Treatments. Neuropharmacology, 69, 62-74. [Google Scholar] [CrossRef] [PubMed]
[32] Pressler, R.M., Boylan, G.B., Marlow, N., et al. (2015) Bumetanide for the Treatment of Seizures in Newborn Babies with Hypoxic Ischaemic Encephalopathy (NEMO, an Open-Label, Dose Finding, and Feasibility Phase 1/2 Trial. The Lancet Neurology, 14, 469-477. [Google Scholar] [CrossRef] 
[33] Thoresen, M. and Sabir, H. (2015) Epilepsy: Neonatal Seizures Still Lack Safe and Effective Treatment. Nature Reviews Neurology, 11, 311-312. [Google Scholar] [CrossRef] [PubMed]
[34] Friedel, P., Kahle, K.T., Zhang, J.W., et al. (2015) WNK1-Regulated Inhibitory Phosphorylation of the KCC2 Cotransporter Maintains the Depolarizing Action of GABA in Immature Neurons. Science Signaling, 8, ra65. [Google Scholar] [CrossRef] [PubMed]
[35] Furukawa, M., Tsukahara, T., Tomita, K., et al. (2017) Neonatal Maternal Separation Delays the GABA Excitatory-to-Inhibitory Functional Switch by Inhibiting KCC2 Expression. Biochemical and Biophysical Research Communications, 493, 1243-1249. [Google Scholar] [CrossRef] [PubMed]
[36] Puskarjov, M., Kahle, K.T., Ruusuvuori, E., et al. (2014) Pharmacotherapeutic Targeting of Cation-Chloride Cotransporters in Neonatal Seizures. Epilepsia, 55, 806-818. [Google Scholar] [CrossRef] [PubMed]
[37] Kim, D.Y., Fenoglio, K.A., Simeone, T.A., et al. (2008) GABAA Receptor-Mediated Activation of L-Type Calcium Channels Induces Neuronal Excitation in Surgically Resected Human Hypothalamic Hamartomas. Epilepsia, 49, 861-871. [Google Scholar] [CrossRef] [PubMed]

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