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Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

DOI: 10.1155/2013/659374

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Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+)-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult. 1. Introduction Hypoxic-ischemic brain damage caused by intrapartum disastrous events is still an important problem in modern obstetrics even in developed countries. It accounts for 10% to 20% of infants with cerebral palsy [1, 2]. Since 1997, we have been performing a regional population-based study on intrauterine fetal deaths, neonatal deaths, and severely handicapped infants [1]. From a total of 140,000 deliveries in the last 13 years, we found a perinatal mortality rate of 4 per 1,000. This is the lowest rate in the world (perinatal mortality includes stillbirths ≥22 weeks of gestation and neonatal deaths ≤7 days of life). However, even where the most advanced perinatal services are available, the incidence of brain damage is 2/1,000, similar to rates around the world [2]. Among infants with brain damage, the most frequent cause is congenital abnormality (1/3), and hypoxic-ischemic encephalopathy constitutes 15%. Thus, it is important for us to study (1) how to predict fetal hypoxic-ischemic events early enough to prevent brain damage, (2) how to treat severely damaged neonates immediately after birth to prevent brain damage, and (3) how to individualize fetuses at high-risk of brain damage? We have been performing clinical and basic animal studies to elucidate the pathogenesis of hypoxic-ischemic brain damage of

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