Expression of c-fos, p53, Transforming Growth Factor-beta1 and Glial Fibrillary Acidic Protein in Hippocampus Following Transient Forebrain Ischemia in Mongolian Gerbil

ABSTRACT

BACKGROUND: Recent studies have shown that delayed neuronal death is closely associated with early gene (c-fos or c-jun)-related apoptosis in addition to hypoxia-induced energy deficiency in the hippocampus. METHODS: To elucidate the role of c-fos, p53, TGF-1 and glial fibrillary acidic protein (GFAP) and their interactions, cellular expression with immunohistochemistry was examined during the time period of 10-minute hypoxia with variable reperfusion intervals in the mongolian gerbil hippocampus. RESULTS: Hippocampal CA1 shows progressive and delayed neuronal damage beginning from the 24-hour reperfusion, while CA2-3 reveals non-progressive, eosinophilic inclusion body within the neuron throughout the time period. CA1 neurons show short-term expressions of c-fos prior to significant cellular damage. However, CA2-3 neurons show persistent expressions by 3-day reperfusion. In both CA1 and CA2-3, p53 is expressed for the short-term period of the early time points. However, its intensity and duration are much less in CA2-3 than in CA1. While TGF-1 is transiently expressed at 24-hour reperfusion in CA1, its expression in CA2-3 is persistent in late time points. Early expression of GFAP is observed in the pyramidal layer of CA1 prior to neuronal damage and progressively increased in the late time points. CONCLUSION: These results suggest that c-fos and TGF-1 may play a role in neuronal viability in the early- and late time points. Astrocytes may also be responsible for the active protective mechanism to neuronal death, as well as reactive gliosis. The hypoxia-induced neuronal damage is, in part, a p53-dependent process in the CA1 neurons.