ICAM-1 upregulation in the spinal cords of PLSJL mice with experimental allergic encephalomyelitis is dependent upon TNF-α production triggered by the loss of blood-brain barrier integrity

Urate (UA) selectively scavenges peroxynitrite-dependent radicals and suppresses CNS inflammation through effects that are manifested at the blood-brain barrier (BBB).ICAM-1 upregulation in the spinal cord tissues of myelin basic protein (MBP) immunized mice is selectively inhibited by UA treatment. In contrast, the expression of ICAM-1 and other adhesion molecules by circulating cells is unchanged. Moreover, TNF-alpha expression in the CNS tissues of MBP-immunized mice is suppressed by UA treatment but TNF-alpha-induced ICAM-1 expression on neurovascular endothelial cells is not. Therefore the effect of UA on ICAM-1 upregulation in the CNS tissues is likely due to its known contribution to the maintenance of BBB integrity in MBP-immunized mice which in turn inhibits cell invasion into the CNS and prevents TNF-a production in CNS tissues. (C) 2004 Elsevier B.V. All rights reserved.