DIFFERENTIAL PERMEABILITY OF THE BBB IN ACUTE EAE - ENHANCED TRANSPORT OF TNF-ALPHA

Impairment of the blood-brain barrier (BBB) in experimental autoimmune encephalomyelitis (EAE) has been frequently attributed to disruption, without much consideration of saturable transport processes. In mice with EAE, we studied the permeability of the BBB to radioactively labe led albumin and sucrose, markers of BBB disruption, and tumor necrosis factor-alpha (TNF-alpha), a cytokine transported across the BBB by a saturable system and thought to play a role in the pathogenesis of EAE . Permeation of the BBB was increased to all three substances during t he acutely ill stage, was greatest in the lumbar spine, and returned t o normal with recovery. The change in BBB permeability to sucrose was greater than to the larger albumin and is consistent with a partial di sruption of the BBB. The enhanced permeability to TNF-alpha was compar able to that for sucrose, even though TNF-alpha is similar in size to albumin. This paradoxically high uptake of TNF-alpha could be explaine d by an enhancement of its endogenous saturable transport system. Thus the changes in BBB function during EAE extend beyond disruption to in clude changes in the saturable transport systems for substances involv ed in the disease process.