Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-κB Signaling Pathway

Abstract

Spinal cord injury (SCI) is a severe neurological trauma that involves complex pathological processes. Inflammatory response and oxidative stress are prevalent during the second injury and can influence the functional recovery of SCI. Specially, Apolipoprotein E (APOE) induces neuronal repair and nerve regeneration, and the deficiency of <i>Apoe</i> impairs spinal cord-blood-barrier and reduces functional recovery after SCI. However, the mechanism by which <i>Apoe</i> mediates signaling pathways of inflammatory response and oxidative stress in SCI remains largely elusive. This study was designed to investigate the signaling pathways that regulate <i>Apoe</i> deficiency-dependent inflammatory response and oxidative stress in the acute stage of SCI. In the present study, <i>Apoe</i>^-/- mice retarded functional recovery and had a larger lesion size when compared to wild-type mice after SCI. Moreover, deficiency of <i>Apoe</i> induced an exaggerated inflammatory response by increasing expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β), and increased oxidative stress by reducing expression of Nrf2 and HO-1. Furthermore, lack of <i>Apoe</i> promoted neuronal apoptosis and decreased neuronal numbers in the anterior horn of the spinal cord after SCI. Mechanistically, we found that the absence of <i>Apoe</i> increased inflammation and oxidative stress through activation of NF-κB after SCI. In contrast, an inhibitor of nuclear factor-κB (NF-κB; Pyrrolidine dithiocarbamate) alleviates these changes. Collectively, these results indicate that a critical role for activation of NF-κB in regulating <i>Apoe</i>-deficiency dependent inflammation and oxidative stress is detrimental to recovery after SCI.