Department of Pediatrics, Yodogawa Christian Hospital, Osaka, Japan.
Department of Pediatrics, Faculty of Medicine, Osaka City University 1-4-3 Asahi-cho, Abeno-ku, Osaka, Japan.
Pediatr Res. 2018 Jan;83(1-2):356-363. doi: 10.1038/pr.2017.260. Epub 2017 Nov 8.
Neonatal ischemic brain injury causes permanent motor-deficit cerebral palsy. Hypoxic-ischemic encephalopathy (HIE) is a very serious condition that can result in death and disability. In 1997, we reported that irreversible neuronal cell damage is induced by the elevation of intracellular Ca ion concentration that has occurred in sequence after excess accumulation of the excitatory neurotransmitter glutamate during ischemia. We also reported that hypothermia was effective in treating ischemic brain damage in rats by suppressing energy loss and raising intracellular Ca ion concentration. Following the 2010 revised International Liaison Committee on Resuscitation guideline, our group developed the Guideline for the treatment of Hypothermia in Japan, and we started online case registry in January 2012. However, therapeutic hypothermia must be initiated within the first 6 h after birth. By contrast, cell therapy may have a much longer therapeutic time window because it might reduce apoptosis/oxidative stress and enhance the regenerative process. In 2014, we administered autologous umbilical cord blood stem cell (UCBC) therapy for neonatal HIE, for the first time in Japan. We enrolled five full-term newborns with moderate-to-severe HIE. Our autologous UCBC therapy is leading to new protocols for the prevention of ischemic brain damage.
新生儿缺血性脑损伤可导致永久性运动功能障碍脑瘫。缺氧缺血性脑病（HIE）是一种非常严重的疾病，可导致死亡和残疾。1997 年，我们报告说，在缺血期间兴奋性神经递质谷氨酸过度积累后依次发生的细胞内 Ca 离子浓度升高，会诱导不可逆的神经元细胞损伤。我们还报告说，通过抑制能量损失和提高细胞内 Ca 离子浓度，低温对治疗大鼠缺血性脑损伤是有效的。根据 2010 年修订的《国际复苏联合会指南》，我们的小组制定了《日本低温治疗指南》，并于 2012 年 1 月开始在线病例登记。然而，治疗性低温必须在出生后 6 小时内开始。相比之下，细胞治疗可能具有更长的治疗时间窗，因为它可能减少细胞凋亡/氧化应激并增强再生过程。2014 年，我们首次在日本为新生儿 HIE 施行了自体脐带血干细胞（UCBC）治疗。我们纳入了五名患有中重度 HIE 的足月新生儿。我们的自体 UCBC 治疗正在为预防缺血性脑损伤制定新的方案。
