Oxidative stress in the human fetal brain: an immunohistochemical study

Because accumulation of oxidative modification products seems to relate to aging and has not been fully studied in fetal brains, an immunohistochemical examination was performed on nine brains ranging from 22-40 weeks of gestation. These brains did not demonstrate lesions except hypoxic-ischemic changes. Advanced glycation end products and 4-hydroxynonenal are generally reported to be negative in neurons of normal young brains, but, in the present study, distinct positive immunoreaction was observed in neurons of fetal brains. Positive immunoreaction appeared earlier in the medulla oblongata than in the cerebrum, and 4-hydroxynonenal began to accumulate earlier than advanced glycation end products. As for glial cells, advanced glycation end products and 4-hydroxynonenal were positive in reactive astrocytes in mid- to late gestation. Because hypoxic-ischemic changes were observed in most of the patients, it is possible that oxidative stress caused by hypoxic-ischemic may be involved in the accumulation of these products in the fetal brain. 8-Hydroxy-2'-deoxyguanosine was negative even in patients demonstrating positive reaction for advanced glycation end products and 4-hydroxynonenal. In the fetal brain, DNA might be strongly protected from oxidative damage. 4-Hydroxynonenal is generally positive in the cytoplasm but was positive in the nucleus of immature neurons and glial cells in the present study, suggesting a unique metabolism of the fetal brain.