Tumor necrosis factor and stroke: Role of the blood-brain barrier

The progression and outcome of stroke is affected by the intricate relationship between the blood-brain barrier (BBB) and tumor necrosis factor a (TNF alpha). TNF alpha crosses the intact 131313 by a receptor-mediated transport system that is upregulated by CNS trauma and inflammation. In this review, we discuss intracellular trafficking and transcytosis of TNF alpha, regulation of TNF alpha transport after stroke, and the effects of TNFa on stroke preconditioning. TNF alpha can activate cytoprotective pathways by pretreatment or persistent exposure to low doses. This explains the paradoxical observation that transport of this proinflammatory cytokine improves the survival and function of hypoxic cells and of mice with stroke. The dual effects of TNF alpha may be related to differential regulation of TNF alpha trafficking downstream to TNFR1 and TNFR2 receptors. As we better understand how peripheral TNF alpha affects its own transport and modulates neuroregeneration, we may be in a better position to pharmacologically manipulate its regulatory transport system to treat stroke. (c) 2007 Elsevier Ltd. All rights reserved.