Selective increase in TNF alpha permeation across the blood-spinal cord barrier after SCI.
We generated a novel mouse model of spinal cord injury (SCI) by hemisection of the right L1 lumbar spinal cord, measured the permeability of the blood-spinal cord barrier (BSCB), and tested the hypothesis that tumor necrosis factor alpha (TNF alpha) penetrates the injured BSCB by an enhanced transport system. SCI produced stereotypical sensorimotor deficits resembling the classically described Brown-Seqúard syndrome. Disruption of the BSCB was reflected by increased spinal cord uptake of radiolabeled albumin from blood; this was transient (immediately after SCI) and confined to the lumbar spinal cord. By contrast, specific increase in the entry of TNF alpha was detected in brain, cervical, thoracic, and lumbar spinal cord at 1 week after SCI, in addition to its immediate and transient increase consistent with barrier disruption. Lack of a second peak of increase in the entry of IL1 beta further supported the specificity of the TNF alpha response. Moreover, enhanced uptake of radiolabeled TNF alpha was suppressed by excess non-radiolabeled TNF alpha, indicating competition of entry via the known transport system for TNF alpha. Therefore, upregulation of the transport system after SCI probably mediates the increased permeation of TNF alpha across the BSCB. Enhanced entry of TNF alpha at 1 week after SCI was concurrent with sensorimotor and gait improvement of the mouse. We conclude that SCI by lumbar hemisection activates the transport system for TNF alpha at the BBB and suggest that selective permeation of TNF alpha may facilitate functional recovery.
Pan
Weihong
W
Department of Medicine and Neuroscience Program, Tulane University School of Medicine and VA Medical Center, New Orleans, LA 70112-1262, USA. wpan@tulane.edu
Zhang
Lihua
L
Liao
Jie
J
Csernus
Balazs
B
Kastin
Abba J
AJ
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D008159:Lumbar Vertebrae; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009416:Nerve Regeneration / Q000276:immunology; D021381:Protein Transport / Q000276:immunology*; D020127:Recovery of Function / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000276:immunology*
D000418:Albumins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha