Genetic ablation of receptor for advanced glycation end products promotes functional recovery in mouse model of spinal cord injury.

Spinal cord injury (SCI) results in a loss of normal motor and sensory function, leading to severe disability and reduced quality of life. The aim of this work was to investigate the effect of receptor for advanced glycation end products (RAGE) deficiency on the function recovery in a mouse model of SCI. Mice received a mid-thoracic spinal contusion injury. Upregulation of RAGE protein expression in spinal cord tissue was evident at 12 h after SCI and continued at 2 and 5 days. Furthermore, we showed that locomotor recovery was improved and lesion pathology was reduced after SCI in RAGE-deficient mice. RAGE deficiency in mice attenuated apoptosis after SCI through inhibiting p53/Bax/caspase-3 pathway. RAGE deficiency in mice inhibited inflammation after SCI, marked by reduced myeloperoxidase activity, NFκB nuclear translocation, and TNF-α, IL-1ß, and IL-6 mRNA and protein levels. RAGE deficiency in mice exposed to SCI suppressed the upregulation of inducible nitric oxide synthase (iNOS) and gp91-phox and attenuated oxidative and nitrosative stresses, marked by reduced formation of malondialdehyde, reactive oxygen species, peroxynitrite (OONO(-)), and 3-nitrotyrosine. RAGE deficiency in mice exposed to SCI attenuated glial scar at the injury site, marked by decreased expression of glial fibrillary acidic protein. These data indicate that the RAGE plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.