Antibodies neutralizing Nogo-A increase pan-cadherin expression and motor recovery following spinal cord injury in rats.

摘要

STUDY DESIGN: A rat model of spinal cord injury was used to test the hypothesis that Nogo-A monoclonal antibody (NEP1-40) promotes morphologic and functional recoveries of injured spinal cord. OBJECTIVE: Nogo-A is a myelin-associated neurite outgrowth inhibitory protein, which blocks elongation nerve fibers and limits neuronal regeneration after central nervous system injury. METHODS: Forty-four rats were utilized and allocated into control (vehicle) and NEP1-40-treated groups. In all animals, the spinal cord was hemi-transected at Th-10 and phosphate-buffered saline solution was immediately applied on the injured area in the control group. NEP1-40 solution was immediately applied on the hemi-transected area in the treatment group. Each group was subdivided into three subgroups according to the postsurgical day of killing (3, 8 and 21 days). The spinal cords were removed for analysis. RESULTS: Motor scores in the NEP1-40-treated groups were significantly higher than those in the vehicle groups both at 8 and 21 days post injury. Immunohistochemical staining for pan-cadherin, a marker of neuronal cell adhesion and axonal sprouting, revealed a significant increase in staining in the NEP1-40 treatment group at 8 and 21 days post injury. Transmission electron microscopical evaluation revealed degeneration of the myelin and loss of cytoarchitectural organization in the axons of controls. Better preservation and normal histologic features were observed in the NEP1-40-treated groups. CONCLUSION: We have demonstrated improved preservation of injured axons and significant pan-cadherin expression after NEP1-40 treatment after the spinal cord injury. Inhibition of Nogo-A may improve the capacity for neuronal regeneration after spinal cord injury.