The presence of glia-derived nexin and glia fibrillary acidic protein (GFAP) was investigated in the hippocampus of Mongolian gerbils (Meriones unguiculatus) after transient forebrain ischemia. Bilateral clamping of the common carotid arteries for 7 min resulted in selective degeneration of CA1 pyramidal cells after a delay of three to four days, the so-called delayed neuronal death. Immunoreactivity for glia-derived nexin was found in astrocytes of all CA1 layers and was detectable until day 90 (the longest survival time studied). Astroglial reactivity was demonstrated in parallel by staining for GFAP. The co-localization of glia-derived nexin and GFAP was confirmed by double immunocytochemistry. Ultrastructural studies showed the exclusive presence of glia-derived nexin in astrocytes, in the vicinity of degenerating and preserved neuronal structures. Perivascular glia was intensely stained, but endothelial cells were devoid of immunoreactivity. Glia-derived nexin is a potent protease inhibitor with in vitro neurite-promoting activity. During adulthood, it is mainly present in the olfactory system, where receptor neurons are constantly being replaced. The ability of astrocytes to renew the expression of glia-derived nexin after selective delayed neuronal death and the prolonged presence of the protease inhibitor in a zone where degeneration occurs in the immediate neighborhood of preserved neuronal elements indicate that glia-derived nexin may play a role in structural rearrangements of the central nervous system.