Transient changes in Fos and GFAP immunoreactivity precede neuronal loss in the rat hippocampus following neonatal anoxia.

Early and delayed neuronal and glial changes in the hippocampus were studied in Wistar rats following neonatal anoxia induced by 100% N2 exposure for 25 min at approximately 30 h postnatally. Sham-treatment induced a transient increase in the number of fos immunoreactive neurons in the CA1, CA2, and CA3 regions, with a peak at 120 min following handling. In contrast, a significant decrease in the number of fos-stained cells was seen in the CA1 and CA2 regions at 120 min after the exposure to anoxia, compared to sham-treatment. At 150 and 240 min increased fos immunoreactivity was detected in the CA2 region of anoxic rats. Enhanced glial fibrillary acidic protein staining was seen at Postnatal Day 7 (P7) in the hippocampus of the rats exposed to neonatal anoxia, while no differences between anoxic and sham-treated animals were observed at later time-points. No alteration in nerve cell density was found at P7, while at P15 and later stages a significant reduction in neuronal density was seen in the CA1 region of anoxic rats. Thus, the rapid induction in hippocampal neuronal activity that followed sham-treatment was blocked by the neonatal anoxia, as revealed by changes in immediate early gene expression. A transient reactive astrocytosis developed in the days after the anoxic insult, followed by a loss of neurons in the CA1 region. The findings indicate that a sequence of specific neuronal and glial alterations takes place in the hippocampus after neonatal anoxia, which finally leads to a detectable, regionally restricted, neuronal loss. Moreover, inhibition in fos protein expression may be an early marker for the anoxic damage in CA1 neurons.