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 s tudied in Wistar rats following neonatal anoxia induced by 100% N-2 ex posure for 25 min at approximately 30 h postnatally. Sham-treatment in duced a transient increase in the number of fos immunoreactive neurons in the CA1, CA2, and CA3 regions, with a peak at 120 min following ha ndling, In contrast, a significant decrease in the number of fos-stain ed cells was seen in the CA1 and CA2 regions at 120 min after the expo sure to anoxia, compared to sham-treatment. At 150 and 240 min increas ed fos immunoreactivity was detected in the CA2 region of anoxic rats, Enhanced glial fibrillary acidic protein staining was seen at Postnat al Day 7 (P7) in the hippocampus of the rats exposed to neonatal anoxi a, while no differences between anoxic and sham-treated animals were o bserved 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-tr eatment was blocked by the neonatal anoxia, as revealed by changes in immediate early gene expression, A transient reactive astrocytosis dev eloped in the days after the anoxic insult, followed by a loss of neur ons in the CA1 region, The findings indicate that a sequence of specif ic neuronal and glial alterations takes place in the hippocampus after neonatal anoxia, which finally leads to a detectable, regionally rest ricted, neuronal loss. Moreover, inhibition in fos protein expression may be an early marker for the anoxic damage in CA1 neurons. (C) 1995 Academic Press, Inc.