Differential regulation of osteopontin receptors, CD44 and the alpha(v) and beta(3) integrin subunits, in the rat hippocampus following transient forebrain ischemia.

We have examined the spatiotemporal regulation of CD44 and the alpha(v)beta(3) integrin subunits, which have been identified as receptors for osteopontin (OPN), in the rat hippocampus following transient forebrain ischemia. Immunoreactivity for CD44 and the integrin subunits, alpha(v) and beta(3), showed characteristic time- and cell-dependent patterns in the ischemic hippocampus. CD44 immunoreactivity was induced at day 1 after reperfusion, reached a peak at day 3, and returned to basal levels by day 7. CD44 was induced in a subset of activated microglial cells within sites of intense neural damage, and the concomitant induction of OPN and CD44 was observed in the same cells in the ischemic hippocampus. In contrast, increased immunoreactivity for alpha(v) and beta(3), which shared overlapping expression patterns in the ischemic hippocampus, occurred in the majority of reactive astrocytes and only a few microglia at day 3 after reperfusion, and was sustained for more than 2 weeks. Immunoreactivity for both integrin subunits colocalized with OPN immunoreactivity in reactive astrocytes, and OPN immunoreactivity was also diffusely localized over the extracellular matrix around the reactive astrocytes. These data indicated that the rapid and transient induction of CD44 and OPN occurred in activated microglia/macrophages, whereas the long-lasting induction of alpha(v) and beta(3) integrin subunits and OPN occurred in reactive astrocytes, suggesting that the multifunctional role of OPN in the ischemic brain may be attributed, in part, to a time- and cell-dependent interaction with CD44 or integrin alpha(v)beta(3).