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

• Published in: Frontiers in cellular neuroscience Vol. 12; p. 142
• Main Authors: Yang, Xuan, Chen, Shurui, Shao, Zhenya, Li, Yuanlong, Wu, He, Li, Xian, Mao, Liang, Zhou, Zipeng, Bai, Liangjie, Mei, Xifan, Liu, Chang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 23.05.2018; Frontiers Media S.A
• Subjects: Apolipoprotein E; Apolipoproteins; Apoptosis; Autophagy; contusive spinal cord injury; Cytokines; IL-1β; Inflammation; Interleukin 6; Kinases; Laboratory animals; neuroinflammation; Neuroscience; Neurosciences; NF-κB protein; Orthopedics; Oxidative stress; Pathogenesis; Peptides; Proteins; Pyrrolidine dithiocarbamate; Recovery of function; Regeneration; Signal transduction; Spinal cord injuries; Trauma; Traumatic brain injury; Tumor necrosis factor-TNF; China; apoptosis; contusive spinal cord injury; Apolipoprotein E; neuroinflammation; oxidative stress
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2018.00142

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 impairs spinal cord-blood-barrier and reduces functional recovery after SCI. However, the mechanism by which 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 deficiency-dependent inflammatory response and oxidative stress in the acute stage of SCI. In the present study, mice retarded functional recovery and had a larger lesion size when compared to wild-type mice after SCI. Moreover, deficiency of 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 promoted neuronal apoptosis and decreased neuronal numbers in the anterior horn of the spinal cord after SCI. Mechanistically, we found that the absence of 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 -deficiency dependent inflammation and oxidative stress is detrimental to recovery after SCI.