Selective increase in TNFα 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 (TNFalpha) penetrates the injured BSCB by an enhanced transport system. SCI produced stereotypical sensorimotor deficits resembling the classically described Brown-Sequard 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 TNFalpha 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 IL1beta further supported the specificity of the TNFalpha response. Moreover, enhanced uptake of radiolabeled TNFalpha was suppressed by excess non-radiolabeled TNFalpha indicating competition of entry via the known transport system for TNFalpha. Therefore, upregulation of the transport system after SCI probably mediates the increased permeation of TNFalpha across the BSCB. Enhanced entry of TNFalpha 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 TNFalpha at the BBB and suggest that selective permeation of TNFalpha may facilitate functional recovery. (C) 2002 Elsevier Science B.V. All rights reserved.