胎児脳障害発生過程を考える : 一過性子宮内虚血と遅発性エネルギー代謝不全

概要

論文の詳細を見る
We speculate that energy failure of fetal brain is caused by uteroplacental ischemia, resulting in fetal brain damage that could lead to cerebral palsy (CP). 1) Clinical research In our prospective study for newborns with low Apgar scores at birth, we found two types of the newborns who developed brain damage afterwards by analyzing their conditions at birth ; asphyxiated and not asphyxiated newborns. Only 5% of the newborns with brain damage were asphyxiated at birth. Majority of the newborns (95%) was not asphyxiated. The clinical characteristics of them without asphyxia were loss of variability of fetal heart rates, oligohydramios and abnormal fetal presentation. The results suggest that antepartum origin is responsible for brain damage of newborns without asphyxia as recent reports suggest. 2) Experimental study (1) Relationship between fetal brain damage and transient uteroplacental ischemia One cause of fetal brain damage is an antepartum hypoxic-ischemic encephalopaty. The primary pathophysiological event in brain ischemia is mitochondrial dysfuncion, so called energy failure. The idea is supported by the study observing concentration of lactate in brain of newborns suffered from hypoxicischemic encephalopathy at birth by using MRS (magnetie resomnance spectrography). The newborns that developed CP at 1 year of age had high concentrations of lactate in their brain. The finding indicates that energy failure in brain closely correlates with deleterious brain damage. We speculate that the initial transient ischemia leads to gradual mitochondrial calcium overload, triggering energy failure and apoptotic or necrotic brain cell death. We undertook experiments to understand relationship between transient uteroplacental ischmemia and mitochondrial respiratory activity as well as ATP and lactate production in fetal rat brain. Transient uteroplacental ischemia of 30 min apparently induced delayed energy failure in fetal forebrain. Following experimental results supported this: 1) Mitochondrial respiratory activity significantly decreased 4 hours after ischemia during reperfusion. At the same time, tissue concentration of ATP decreased while that of lactate increased significantly. 2) Electron-microscopic findings of mitochondria revealed that prominent degeneration of mitochondria appeared in fetal forebrain 4 hours after ischemia. Furthermore the abnormal electron-microscopic findings of mitochondria and altered mitochondrial respiratory activity were improved by administration of cyclosporin A to pregnant dams after the ischemia. Since cycrosporin A is known to block a deleterious permeability transition in mitochondrial membrane in response to calcium overload and oxidative stress, the effects of cyclosporin A supports a mitochondrial origin for this delayed energy failure in fetal forebrain. (2) Developmental changes in energy metabolism of rats during perinatal period. From 14 days of gestation to term (21 days of gestation), we found gradual maturation of oxidative metabolism of mitochondria that was initiated in late gestation, together with a marked increase in ATP concentration and a marked reduction in lactate concentration. The highest rate of mitochondrial respiration was observed in 1-hour-old pups. These results indicate that, in the rat brain, acceleration in mitochondrial respiration occurs immediately after birth in order to maintain high-energy phosphate levels. And this may be crucial for the successful outcome in adaptation for extrauterine life of the newborn. 3) Hypothesis Based on these results, we establish a following hypothesis ; if the energy failure of fetal developing brain occurs by transient uteroplacental ischemia, the newborn brain is unable to maintain high-energy phosphate levels immediately after birth. This may result in deleterious brain damage like CP of newborns. Further investigation should be necessary to clarify the hypothesis.
社団法人日本産科婦人科学会の論文
2002-08-01

胎児脳障害発生過程を考える : 一過性子宮内虚血と遅発性エネルギー代謝不全

スポンサーリンク

概要

著者

関連論文

スポンサーリンク