TRAUMATIC SPINAL-CORD INJURY INDUCES NUCLEAR FACTOR-KAPPA-B ACTIVATION

Citation
Jr. Bethea et al., TRAUMATIC SPINAL-CORD INJURY INDUCES NUCLEAR FACTOR-KAPPA-B ACTIVATION, The Journal of neuroscience, 18(9), 1998, pp. 3251-3260
Citations number
55
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0270-6474
Volume
18
Issue
9
Year of publication
1998
Pages
3251 - 3260
Database
ISI
SICI code
0270-6474(1998)18:9<3251:TSIINF>2.0.ZU;2-V
Abstract
Inflammatory responses are a major component of secondary injury and p lay a central role in mediating the pathogenesis of acute and chronic spinal cord injury (SCI). The nuclear factor-kappa B (NF-kappa B) fami ly of transcription factors is required for the transcriptional activa tion of a variety of genes regulating inflammatory, proliferative, and cell death responses of cells. In this study we examined the temporal and cellular expression of activated NF-kappa B after traumatic SCI. We used a contusion model (N.Y.U. Impactor) to initiate the early bioc hemical and molecular changes that occur after traumatic injury to rep roduce the pathological events associated with acute inflammation afte r SCI. The activation and cellular distribution of activated NF-kappa B was evaluated by using a monoclonal antibody that selectively recogn izes activated p65 in a NF-kappa B dimer. Immunohistochemical and West ern blot analyses demonstrated that NF-kappa B activation occurred as early as 0.5 hr postinjury and persisted for at least 72 hr. Using ele ctrophoretic mobility shift assays (EMSA), we demonstrate that NF-kapp a B is activated after SCI. In our immunohistochemical, Western, and E MSA experiments there are detectable levels of activated NF-kappa B in our control animals. Using double-staining protocols, we detected act ivated NF-kappa B in macrophages/microglia, endothelial cells, and neu rons within the injured spinal cord. Colocalization of activated NF-ka ppa B with the NF-kappa B-dependent gene product, inducible nitric oxi de synthase (iNOS), suggests functional implications for this transcri ption factor in the pathogenesis of acute spinal cord injury. Although there is considerable evidence for the involvement of an inflammatory reaction after traumatic SCI, this is the first evidence for the acti vation of NF-kappa B after trauma. Strategies directed at blocking the initiation of this cascade may prove beneficial as a therapeutic appr oach for the treatment of acute SCI.