title: Transient changes in Fos and GFAP immunoreactivity precede neuronal loss in the rat hippocampus following neonatal anoxia.
abstract: 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.
authors.affiliation: Institute of Human Physiology, Catholic University, Rome, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Dell'Anna
authors.forename: M C
authors.initials: MC
authors.lastname: Geloso
authors.forename: G
authors.initials: G
authors.lastname: Draisci
authors.forename: J
authors.initials: J
authors.lastname: Luthman
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis*; D006624:Hippocampus / Q000737:chemistry* / Q000473:pathology*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D009474:Neurons / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D051381:Rats
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016760:Proto-Oncogene Proteins c-fos