Temporal and regional patterns of Smad activation in the rat hippocampus following global ischemia

In this study, we examined the temporal and regional patterns of Smad activation in the rat hippocampus following global ischemia. We also examined the association between Smad activation and ischemia-induced pathology in the hippocampus. We found that 1) Smad1, -2, -3, and -5 proteins were detected in the rat hippocampus by means of western blot and immunohistochemistry; 2) after 5 min of ischemia, Smad2 and Smad3 proteins accumulated in the nuclei of pyramidal cells in the CA1 region, which is vulnerable to ischemia; 3) after 3 min of ischemia, which was non-lethal, there was no such nuclear accumulation of Smad2 and Smad3 in the CA1 region; 4) following injection of activin A, nuclear accumulation of Smad2 and Smad3 was induced not only in pyramidal cells of the CA1 region, but also in pyramidal cells of the CA3 region as well as in granule cells of the DG region; 5) activin A-induced nuclear accumulation of Smad2 and Smad3 neither caused degeneration of hippocampal neurons nor prevented degeneration induced by ischemia. These results suggest that in the hippocampus, ischemia-induced activation of Smad2 and Smad3 is associated with the response to stress but is not related to neuronal survival or death.