Transient microglial and prolonged astroglial upregulation of osteopontin following transient forebrain ischemia in rats.

Osteopontin (OPN) is an adhesive glycoprotein linked to a variety of pathophysiological processes, with neuroprotective properties in ischemic injury. We examined the postischemic expression and localization of OPN in the rat brain after transient forebrain ischemia. The semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that OPN expression in the hippocampal CA1 region was biphasic, peaking at day 3 after reperfusion and again between days 14 and 28. The two phases of OPN induction occurred in a time- and cell-dependent manner in the ischemic hippocampus. OPN mRNA expression in activated microglia was first induced 1 day after reperfusion, reached a peak at 3 days, and returned to basal levels by 7 days. In contrast, OPN expression in reactive astrocytes was first induced by 10 days after reperfusion in the hippocampal CA1. Astroglial OPN expression further increased, reaching a peak at day 14 and was maintained up to day 28, the latest time point we examined. OPN immunoreactivity in the ischemic hippocampus matched the mRNA induction patterns. OPN protein was first localized in the astroglial cytoplasm and later in the extracellular matrix of the hippocampal CA1. The temporal and cellular patterns of OPN induction in the ischemic hippocampus suggest a multifunctional capacity in the pathogenesis of ischemic injury, with the increased OPN production and secretion by reactive astrocytes being involved in subsequent tissue repair and reorganization.