Wh. Pan et al., Upregulation of tumor necrosis factor alpha transport across the blood-brain barrier after acute compressive spinal cord injury, J NEUROSC, 19(9), 1999, pp. 3649-3655
Tumor necrosis factor alpha (TNF) is a cytokine that is involved in the inf
lammatory process after CNS injury and is implicated in neuroregeneration.
A saturable transport system for TNF located at the blood-brain barrier (BB
B) is responsible for the limited entry of TNF from blood to the CNS in nor
mal mice.
After partial disruption of the BBB by compression of the lumbar spinal cor
d, permeability to TNF was increased not only in the lumbar spinal cord but
also in brain and distal spinal cord segments, where the BBB remained inta
ct. The increase in the entry of TNF to the CNS followed a biphasic tempora
l pattern, with a first peak immediately after injury and a second peak sta
rting on day 3; these changes lasted longer than the mere disruption of the
BBB. The increased entry of TNF was abolished by addition of excess unlabe
led TNF, showing that the transport system for TNF remained saturable after
spinal cord injury (SCI) and providing evidence that the enhanced entry of
TNF could not be explained by diffusion or leakage.
This study adds strong support for our concept that the saturable transport
system for TNF across the BBB can be upregulated in the diseased state, an
d it suggests that the BBB is actively involved in the modulation of the pr
ocesses of degeneration and regeneration after SCI.