Early c-Fos induction after cerebral ischemia: A possible neuroprotective role

The role of c-Fos in neurodegeneration or neuroprotection after cerebral is chemia is controversial. To investigate whether early c-Fos induction after ischemia is associated with neuroprotection. rats were subjected to 10 min utes of transient forebrain ischemia and c-Fos expression was examined. Res istant dentate granule cells and neurons in CA2-4 displayed more robust imm unoreactivity than vulnerable neurons in the CAI region of hippocampus duri ng early hours of reperfusion. By 6 hours after reperfusion. c-Fos immunore activity was greatly diminished in all areas of the hippocampus. Administra tion of N-acetyl-O-methyldopamine (NAMDA), a compound previously shown to p rotect CAI neurons against ischemia, increased c-Fos immunoreactivity in th e CA1 vulnerable region at 6 hours after ischemia and protected SK-N-BE(2)C neurons from oxygen glucose deprivation. Further in vitro study showed tha t NAMDA potentiated phorbol-12 myristate-13 acetate (PMA)-induced c-Fos exp ression, API binding activity, and late gene expression determined by chlor amphenicol acetyltransferase (CAT) activity from API containing tyrosine hy droxylase promoter-CAT fusion gene in SK-N-BE(2)C neurons. In vivo and in v itro results showed that a neuroprotectant, NAMDA, in concert with another stimulus (for example, ischemia or PMA) up-regulates c-Fos expression and s uggested that the early rise of NAMDA-induced c-Fos expression in vulnerabl e CA1 neurons may account for neuroprotection by means of up-regulating lat e gene expression for survival.