発育・分化の異常からみた周産期脳障害の発生とそのメカニズム(<特集>第56回学術講演会シンポジウム1 : 胎児の発育・分化とその異常)
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Perinatal brain damage is an exemplary disease entailing both childhood and adult neurological pathologies. The purposes of this study were to evaluate the epidemiology of perinatal brain damage in Miyazaki prefecture and to investigate the pathophysiology of asphyxia-induced damage in an animal model. One hundred and nine cases of perinatal brain damage were registered in Miyazaki prefecture from 1998 to 2002, in which 1% of all births in Japan during this period. We arbitrarily categorized cases into seven groups according to the main cause of brain damage: (1) asphyxia 20%, (2) prematurity 19%, (3) congenital anomalies 21%, (4) IUGR 12%, (5) TORCH 4%, (6) PVL 13%, and (7) miscellaneous and unknown causes 11%. Correlational analysis of the intrapartum fetal heart rate pattern revealed that 75% of the nonasphyxia-related cases showed a non-reassuring pattern, which could have led to the misdiagnosis of intrapartum hypoxia-asphyxia and litigation cases. To elucidate the mechanisms by which asphyxia induces brain damage in the perinatal period, we experimentally induced hypoxia-ischemia (HI) in fetal sheep and neonatal rats. Partial umbilical occlusion of chronically instrumented fetal lambs showed the severity and duration of arterial hypotension to be the most important factor causing brain damage. A model of Hi-induced brain damage in neonatal rats was strongly associated with disruption in the blood-brain barrier and neuronal injury. "Hypoxic-ischemic tolerance" phenomenon is associated with induction of heat shock protein-72 in endothelial cells in the brain. Considering that the immature neuron is more resistant to hypoxia-ischemia than the mature cell, we conclude that damage to the fetal and neonatal brain is caused by a failure of homeostasis in the cardiac and circulatory systems, which we have named the "weak assisted and second player (WASP) theory" We induced HI in the rat at postnatal day 7 and observed long-term changes in behavior and brain histology. We found slowly progressive neuronal damage that began five weeks after the HI insult, although we found compensatory enlargement of the contralateral cerebral hemisphere until that time. We observed evidence of histological damage and impairment of cognitive and behavioral functions such as learning and memory. Our further studies showed that this slowly progressive neuronal damage could be aggravated by seclusion and relieved by rehabilitation. Edaravone, the first choice of drug for adult cerebral infarction in Japan, showed a significant histological and behavioral effects in dose-response manner when applied just after HI insult. Glial cell line-derived neurotrophic factor (GDNF) also had a significant neuroprotective effect.
- 社団法人日本産科婦人科学会の論文
- 2004-09-01
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