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-κB) 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 10 g) 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-κB, the mRNA and protein levels of TNF-α and MMP-9, and the enzyme activity of MMP-9. Nrf2 (−/−) mice were demonstrated to have more spinal cord edema, NF-κB 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-κB activity, TNF-α, and MMP-9 in spinal cord after SCI.
Highlights
Spinal cord injury (SCI) initiates a series of cellular and molecular cascade events and that a combination of secondary injury factors leads to a progressive neuronal injury [1]
We evaluated the effect of Nuclear factor erythroid 2-related factor 2 (Nrf2) genotype on the activation of NF-κB, tumor necrosis factor-α (TNF-α), and Matrix metalloproteinase-9 (MMP-9) in spinal cord after SCI
We found that the mice lacking Nrf2 function have significantly enhanced secondary spinal cord injury characterized by increased spinal cord edema and severer inflammatory response
Summary
Spinal cord injury (SCI) initiates a series of cellular and molecular cascade events and that a combination of secondary injury factors leads to a progressive neuronal injury [1]. The proinflammatory cytokine TNF-α, which is upregulated immediately after SCI, can enhance vascular permeability [7]. MMP-9 is upregulated in leucocytes entering the spinal cord, directly facilitating their extravasation, and promoting the tissue damage that they caused [9, 10].
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