Upregulation of tumor necrosis factor alpha transport across the blood-brain barrier after acute compressive spinal cord injury.
Tumor necrosis factor alpha (TNF) is a cytokine that is involved in the inflammatory process after CNS injury and is implicated in neuroregeneration. A saturable transport system for TNF located at the blood-brain barrier (BBB) is responsible for the limited entry of TNF from blood to the CNS in normal mice. After partial disruption of the BBB by compression of the lumbar spinal cord, 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 intact. The increase in the entry of TNF to the CNS followed a biphasic temporal pattern, with a first peak immediately after injury and a second peak starting 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 unlabeled 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, and it suggests that the BBB is actively involved in the modulation of the processes of degeneration and regeneration after SCI.
Pan
W
W
Department of Neurology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Kastin
A J
AJ
Bell
R L
RL
Olson
R D
RD
D000818:Animals; D001812:Blood-Brain Barrier; D006614:Hindlimb; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity; D012018:Reflex; D013117:Spinal Cord Compression; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha