Expression of syndecan-2 in the amoeboid microglial cells and its involvement in inflammation in the hypoxic developing brain.

The present study examined the expression of heparan sulphate proteoglycan, syndecan-2 (Sdc-2) in the corpus callosum and the amoeboid microglial cells (AMC) in the neonatal rat brain in response to hypoxia. In 1-day old Wistar rats subjected to hypoxia the mRNA and protein expression of Sdc-2 in the corpus callosum, heavily populated by AMC, was increased up to 3 days after the hypoxic exposure. Immunoexpression of Sdc-2 was localized in AMC as confirmed by double labeling using microglial marker. Primary cultures of microglial cells subjected to hypoxia showed a significant increase in Sdc-2 expression. Application of Sdc-2 to microglial cultures under hypoxia increased the release of tumor necrosis factor-alpha, interleukin-1beta, chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-X-C motif) ligand 12 (CXCL12) by the microglial cells. Additionally, Sdc-2 enhanced the production of reactive oxygen species (ROS) by microglia subjected to hypoxia. Edaravone [3-methyl-1phenyl-2-pyrazolin-5-one], an antioxidant drug, suppressed the hypoxia- and Sdc-2-induced increased production of cytokines, chemokines, and ROS. In the light of these findings, we suggest that Sdc-2 plays an important role in microglial production of inflammatory cytokines, chemokines, and ROS in hypoxic conditions. In this connection, edaravone suppressed the hypoxia- and Sdc-2-induced increased cytokine and ROS production suggesting its therapeutic potential in ameliorating neuroinflammation.