Disruption of Nrf2 enhances the upregulation of nuclear factor-kappaB activity, tumor necrosis factor- α, and matrix metalloproteinase-9 after spinal cord injury in mice

Abstract

Matrix metalloproteinase-9 (MMP-9) plays an important role in the acute periods of spinal cord injury (SCI), and its expression is related to the inflammation which could cause the disruption of the blood-spinal barrier (BBB). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in upregulating of nuclear factor kappa B (NF- B) activity, tumor necrosis factor-α (TNF-α ), and MMP-9 after SCI. Wild-type Nrf2 (+/+) and Nrf2-deficient (Nrf (-/-)) mice were subjected to an SCI model induced by the application of vascular clips (force of 10g) to the dura after a three-level T8-T10 laminectomy. We detected the wet/dry weight ratio of impaired spinal cord tissue, the activation of NF- B, the mRNA and protein levels of TNF- and MMP-9, and the enzyme activity of MMP-9. Nrf2 (-/-) mice were demonstrated to have more spinal cord edema, NF-κ B activation, TNF-α production, and MMP-9 expression after SCI compared with the wild-type controls. The results suggest that Nrf2 may play an important role in limiting the upregulation of NF-α B activity, TNF-α , and MMP-9 in spinal cord after SCI. © 2010 Lei Mao et al.