新生儿缺氧缺血性脑病治疗进展
Progress in Treatment of Neonatal Hypoxic-Ischemic Encephalopathy
DOI: 10.12677/IJPN.2014.31001, PDF, HTML, 下载: 3,091  浏览: 12,822 
作者: 谢东可：泸州医学院附属医院小儿外科，泸州；陈 娟：四川大学华西第二医院新生儿科，成都；张德双*：泸州医学院附属医院新生儿科，泸州
关键词: 新生儿；婴儿；缺氧缺血性脑病；治疗；Neonates； Infants； Hypoxic-Ischemic Encephalopathy； Treatment
摘要: 新生儿缺氧缺血性脑病(HIE)是由围产期窒息引起的，其中，重度HIE为新生儿死亡及儿童致残的重要原因之一。近年来，随着对新生儿HIE发病机制研究的不断深入，其治疗研究亦在不断发展与进步，并为新生儿HIE的治疗带来了新的希望。现就本病的治疗进展予以综述。
Abstract: Hypoxic-ischemic encephalopathy (HIE) in neonates is caused by perinatal asphyxia; severe HIE is one of the important reasons which can result in death during the newborn period and permanent neuropsychological handicaps. In recent years, with the deepening of the pathogenesis research on neonatal HIE, the treatment research is also in constant development and progress, and brings new opportunity for the treatment of neonatal HIE. Now, we will review the progress in treatment of neonatal hypoxic-ischemic encephalopathy.
文章引用：谢东可, 陈娟, 张德双. 新生儿缺氧缺血性脑病治疗进展[J]. 国际神经精神科学杂志, 2014, 3(1): 1-6. http://dx.doi.org/10.12677/IJPN.2014.31001

参考文献

[1] Shankaran, S. (2012) Hypoxic-ischemic encephalopathy and novel strategies for neuroprotection. Clinics in Perinatology, 39, 919929.
[2] Kim, J.J., Buchbinder, N., Ammanuel, S., et al. (2013) Costeffective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy. Medical Devices (Auckland), 6, 1-10.
[3] Vento, M., Asensi, M., Sastre, J., et al. (2003) Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen. Journal of Pediatrics, 142, 240-246.
[4] Nakka, V.P., Gusain, A., Mehta, S.L., et al. (2008) Molecular mechanisms of apoptosis in cere-bral ischemia: Multiple neuroprotective opportunities. Molecular Neu-robiology, 37, 7-38.
[5] Zhang, F., Yin, W. and Chen, J. (2004) Apoptosis in cerebral ischemia: Executional and regulatory signaling mechanisms. Neurological Research, 26, 835-845.
[6] Volpe, J.J. (2008) Neurology of the newborns. 15th Edition, Saunders, 448-461.
[7] Taeusch, H.W., Ballard, R. and Gleason, C. (2005) Avery’s diseases of the newborn. 8th Edition, Saunders, 969-987.
[8] McGuire, W., Fowlie, P.W. and Evans, D.J. (2004) Naloxone for preventing morbidity and mortality in newborn infants of greater than 34 weeks’ gestation with suspected perinatal asphyxia. Cochrane Database of Systematic Reviews, 1, CD003955.
[9] 母得志 (2011) 新生儿缺氧缺血性脑病的诊断和治疗. 实用儿科临床杂志, 14, 1144-1147.
[10] Alkharfy, T.M. (2013) Induced hypothermia to treat neonatal hypoxic-ischemic encephalopathy. Review of literature with metaanalysis and development of national protocol. Neuros-ciences (Riyadh), 18, 18-26.
[11] Orozco-Gutierrez, A., Rojas-Cerda, L., Estrada, R.M., et al. (2010) Hyperbaric oxygen in the treatment of asphyxia in two newborn infants. Diving and Hyperbaric Medicine, 40, 218-220.
[12] 李月凤, 姜毅 (2006) 神经节苷脂GM1治疗新生儿缺氧缺血性脑病疗效观察. 中国新生儿杂志, 21, 5-8.
[13] Wachtel, E.V. and Hendricks-Muñoz, K.D. (2011) Current management of the infant who presents with neonatal encephalopathy. Current Problems in Pediatric and Adolescent Health Care, 41, 132-153.
[14] Jacobs, S.E., Morley, C.J., Inder, T.E., et al. (2011) Whole-body hypothermia for term and near-term newborns with hypoxicischemic encephalopa-thy: A randomized controlled trial. Archives of Pediatrics Adolescent Medicine, 165, 692-700.
[15] Simbruner, G., Mittal, R.A., Rohlmann, F., et al. (2010) Systemic hypothermia after neonatal encephalopathy: Outcomes of neo. nEURO. Network RCT. Pediatrics, 126, e771-e778.
[16] Shankaran, S., Pappas, A., Laptook, A.R., et al. (2008) Outcomes of safety and effectiveness in a multicenter rando-mized, controlled trial of whole-body hypothermia for neonatal hypoxicischemic encephalopathy. Pediatrics, 122, e791-e798.
[17] Rutherford, M., Ramenghi, L.A., Edwards, A.D., Brocklehurst, P., Halliday, H., Levene, M., Strohm, B., Thoresen, M., Whitelaw, A. and Azzopardi, D. (2010) Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: A nested substudy of a randomised controlled trial. Lancet Neurology, 9, 39-45.
[18] 刘玲, 杨于嘉, 文秋生, 王鸿娟, 王多德 (2005) 高压氧治疗对新生大鼠缺氧缺血性脑损伤模型的保护作用. 实用儿科临床杂志, 6, 531-532.
[19] Badr, A.E., Yin, W., Mychaskiw, G. and Zhang, J.H. (2001) Dual effect of HBO on cerebral infarction in MCAO rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 280, R766-R770.
[20] Sunami, K., Takeda, Y., Hashimoto, M. and Hirakawa, M. (2000) Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery. Critical Care Medicine, 28, 2831-2836.
[21] Yang, Z.J., Xie, Y., Bosco, G.M., Chen, C. and Camporesi, E.M. (2010) Hyperbaric oxygenation alleviates MCAO-induced brain injury and reduces hydroxyl radical formation and glutamate release. European Journal of Applied Physiology, 108, 513-522.
[22] Jadhav, V., Ostrowski, R.P., Tong, W., Matus, B., Chang, C. and Zhang, J.H. (2010) Hyperbaric oxygen preconditioning reduces postoperative brain edema and improves neurological outcomes after surgical brain injury. Acta Neurochirurgica Supplementum, 106, 217-220.
[23] Li, J.S., Zhang, W., Kang, Z.M., Ding, S.J., Liu, W.W., Zhang, J.H., Guan, Y.T. and Sun, X.J. (2009) Hyperbaric oxygen preconditioning reduces ischemia-reperfusion injury by inhibition of apoptosis via mitochondrial pathway in rat brain. Neuroscience, 159, 1309-1315.
[24] Liu, Z., Xiong, T. and Meads, C. (2006) Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: Systematic review of Chinese literature. British Medical Journal, 333, 374.
[25] Gould, L.J., Leong, M. and Mushkudiani, I. (2003) Hyperbaric oxygen delays healing in an ischemic wound model. Journal of Surgical Research, 114, 262.
[26] Manzoni, P., Farina, D., Maestri, A., Giovannozzi, C., Leo-nessa, M.L., Arisio, R. and Gomirato, G. (2007) Mode of delivery and threshold retinopathy of prematurity in pre-term ELBW neonates. Acta Paediatrica, 96, 221-226.
[27] Zhang, J.Z., Jing, L., Ma, Y., Guo, F.Y., Chang, Y. and Li, P.A. (2010) Monosialotetrahexosy-1 ganglioside attenuates diabetesenhanced brain damage after transient forebrain ischemia and suppresses phosphorylation of ERK1/2 in the rat brain. Brain Research, 1344, 200-208.
[28] Ohmi, Y., Tajima, O., Ohkawa, Y., Mori, A., Sugiura, Y., Furukawa, K. and Furukawa, K. (2009) Gan-gliosides play pivotal roles in the regulation of complement systems and in the maintenance of integrity in nerve tissues. Proceedings of the National Academy of Sciences of the United States of America, 106, 22405-22410.
[29] Wei, J., Fujita, M., Nakai, M., Waragai, M., Seki-gawa, A., Sugama, S., et al. (2009) Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synuclei-nopathies. American Journal of Pathology, 174, 1891-1909.
[30] Qi, R., Mullen, D.G., Baker, J.R. and Banaszak Holl, M.M. (2010) The mechanism of polyplex internalization into cells: Testing the GM1/caveolin-1 lipid raft mediated endocytosis pathway. Molecular Pharmaceutics, 7, 267-279.
[31] Zhang, Y.P., Huang, Q.L., Zhao, C.M., Tang, J.L. and Wang, Y.L. (2011) GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia. Brazilian Journal of Medical and Biological Re-search, 44, 553561.
[32] Chen, J., Lin, L.X., Ma, B., et al. (2012) Meta-analysis of ganglioside treatment for hypoxic-ischemic encephalopathy in newborn infants. Journal of Applied Clinical Pediatrics, 27, 132135.
[33] Yis, U., Kurul, S.H., Kumral, A., Tuğyan, K., Cilaker, S., Yılmaz, O., Genç, Ş. and Genç, K. (2008) Effect of erythropoietin on oxygen-induced brain injury in the newborn rat. Neuroscience Letters, 448, 245-249.
[34] Iwai, M., Cao, G., Yin, W., Stetler, R.A., Liu, J.L. and Chen, J. (2007) Erythropoietin promotes neuronal replacement through revascularization and neurogenesis after neonatal hypoxia/ischemia in rats. Stroke, 38, 2795-2803.
[35] Shang, Y., Wu, Y., Yao, S., Wang, X.J., Feng, D. and Yang, W.Q. (2007) Protective effect of erythropoietin against ketamine-induced apoptosis in cultured rat cortical neurons: Involvement of PI3K/Akt and GSK-3 beta pathway. Apoptosis, 12, 2187-2195.
[36] Juul, S.E., Beyer, R.P., Bammler, T.K., McPherson, R.J., Wilkerson, J. and Farin, F.M. (2009) Microarray analysis of highdose recombinant erythropoietin treatment of unilateral brain injury in neonatal mouse hippocampus. Pediatric Research, 65, 485-492.
[37] Zhu, C.L., Kang, W.Q., Xu, F.L., Cheng, X.Y., Zhang, Z., Jia, L.T., et al. (2009) Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics, 124, e218-e226.
[38] Elmahdy, H., El-Mashad, A.R., El-Bahrawy, H., El-Gohary, T., El-Barbary, A. and Aly, H. (2010) Human recombinant erythropoietin in asphyxia neonatorum: Pilot trial. Pediatrics, 125, e1135e1142.
[39] Wu, Y.W., Bauer, L.A., Ballard, R.A., Ferriero, D.M., Glidden, D.V., Mayock, D.E., et al. (2012) Erythropoietin for neuroprotection in neonatal encephalopathy: Safety and pharmacokinetics. Pediatrics, 130, 683-691.
[40] Ichiba, H., Tamai, H., Negishi, H., Ueda, T., Kim, T.J., Sumida, Y., et al. (2002) Rando-mized controlled trial of magnesium sulfate infusion for severe birth asphyxia. Pediatrics International, 44, 505-509.
[41] Legido, A., Valencia, I., Katsetos, C.D. and Delivoria-Papadopoulos, M. (2007) Neuroprotection in perinatal hypoxic-ischemic encephalopathy. Effective treatment and future perspectives. Medicina (B Aires), 67, 543-555.
[42] Mobley III, L.W. and Agrawal, S.K. (2003) Role of calcineurin in calcium-mediated hypoxic injury to white matter. Spine Journal, 3, 11-18.
[43] Cuzzocrea, S., Mazzon, E., Costantino, G., Serraino, I., Dugo, L., Calabrò, G., Cucinotta, G., De Sarro, A. and Caputi, A.P. (2000) Beneficial effects of n-acetylcysteine on ischaemic brain injury. British Journal of Pharmacology, 130, 1219-1226.
[44] Noor, J.I., Ueda, Y., Ikeda, T. and Ikenoue, T. (2007) Edaravone inhibits lipid peroxidation in neonatal hypoxic-ischemic rats: An in vivo microdialysis study. Neuroscience Letters, 414, 5-9.
[45] Noor, J.I., Ikeda, T., Ueda, Y. and Ikenoue, T. (2005) A free radical scavenger, edaravone, inhibits lipid peroxidation and the pro-duction of nitric oxide in hypoxic-ischemic brain damage of neonatal rats. American Journal of Obstetrics & Gynecology, 193, 1703-1708.
[46] Gunes, T., Ozturk, M.A., Koklu, E., Kose, K. and Gunes, I. (2007) Effect of allopurinol supplementation on nitric oxide levels in asphyxiated newborns. Pediatric Neurology, 36, 17-24.
[47] Chaudhari, T. and McGuire, W. (2012) Allopurinol for preventing mortality and morbidity in newborn infants with hypoxici-schemic encephalopathy. Cochrane Database of Systematic Reviews, 7, Article ID: CD006817.
[48] Walberer, M., Nedelmann, M., Ritschel, N., Mueller, C., Tschernatsch, M., Stolz, E., Bachmann, G., Blaes, F. and Gerriets, T. (2010) Intravenous immunoglobulin reduces infarct volume but not edema formation in acute stroke. Neuroimmunomodu-lation, 17, 97-102.
[49] Arumugam, T.V., Tang, S.C., Lathia, J.D., Cheng, A.W., Mughal, M.R., Chigurupati, S., et al. (2007) Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proceedings of the National Academy of Sciences of the United States of America, 104, 14104-14109.
[50] 许建文, 陈艳霞 (2008) 大剂量免疫球蛋白治疗重度新生儿缺氧缺血性脑病的效果. 实用儿科临床杂志, 2, 140-141.
[51] Miyake, K., Yamamoto, W., Tadokoro, M., Takagi, N., Sasakawa, K., Nitta, A., Furukawa, S. and Takeo, S. (2002) Alterations in hippocampal GAP-43, BDNF, and L1 following sustained cerebral ischemia. Brain Research, 935, 24-31.
[52] Tyler, W.J. and Poz-zo-Miller, L.D. (2001) BDNF enhances quantal neurotransmitter re-lease and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. Journal of Neuroscience, 21, 4249-4258.
[53] 尹晓娟, 刘冬云, 罗分平, 龙琦, 封志纯 (2009) 碱性成纤维细胞生长因子对缺氧缺血性脑损伤新生鼠骨形态发生蛋白4及其mRNA表达的影响. 中华儿科杂志, 11, 856-861.
[54] Lin, S., Fan, L.W., Rhodes, P.G. and Cai, Z. (2009) Intranasal administration of IGF-1 attenuates hypoxic-ischemic brain injury in neonatal rats. Experimental Neurology, 217, 361-370.
[55] 王海燕, 朱晓峰, 王丽敏, 等 (2008) 脑源性神经营养因子及神经干细. 胞移植治疗新生大鼠缺氧缺血性脑损伤的实验研究. 中华儿科杂志, 7, 544-549.
[56] 栾佐，尹国才，胡晓红, 等 (2005) 人神经干细胞移植治疗重度新生儿缺氧缺血性脑病一例. 中华儿科杂志, 8, 580-583.
[57] 栾佐, 刘卫鹏, 屈素清, 等 (2011) 人神经前体细胞移植治疗新生儿获得性脑损伤的临床观察. 中华儿科杂志, 6, 445-450.
[58] Ma, J., Wang, Y., Yang, J., Yang, M., Chang, K.A., Zhang, L., Jiang, F., Li, Y., Zhang, Z., Heo, C. and Suh, Y.H. (2007) Treatment of hypoxic-ischemic encephalopathy in mouse by transplantation of embryonic stem cell-derived cells. Neurochemistry International, 51, 57-65.
[59] 刘洋, 张萱, 代英, 等 (2008) 骨髓间充质干细胞对缺氧缺血性脑损伤新生大鼠学习记忆功能的重建作用. 中华儿科杂志, 9, 648-653.
[60] Wei, X., Du, Z., Zhao, L., Feng, D., Wei, G., He, Y., et al. (2009) IFATS collection: The conditioned media of adipose stromal cells protect against hypoxia-ischemia-induced brain damage in neonatal rats. Stem Cells, 27, 478-488.