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Tlr4 Deletion Modulates Cytokine and Extracellular Matrix Expression in Chronic Spinal Cord Injury, Leading to Improved Secondary Damage and Functional Recovery.
Ryan, Fari; Francos-Quijorna, Isaac; Hernández-Mir, Gerard; Aquino, Catharine; Schlapbach, Ralph; Bradbury, Elizabeth J; David, Samuel.
Afiliação
  • Ryan F; Centre for Research in Neuroscience and BRaIN Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada.
  • Francos-Quijorna I; The Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
  • Hernández-Mir G; Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London E1 2AT, United Kingdom.
  • Aquino C; Functional Genomics Center Zurich, ETH Zurich and University of Zurich, Zurich 8057, Switzerland.
  • Schlapbach R; Functional Genomics Center Zurich, ETH Zurich and University of Zurich, Zurich 8057, Switzerland.
  • Bradbury EJ; The Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
  • David S; Centre for Research in Neuroscience and BRaIN Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada sam.david@mcgill.ca.
J Neurosci ; 44(6)2024 02 07.
Article em En | MEDLINE | ID: mdl-38326029
ABSTRACT
Toll-like receptors (TLRs) play an important role in the innate immune response after CNS injury. Although TLR4 is one of the best characterized, its role in chronic stages after spinal cord injury (SCI) is not well understood. We examined the role of TLR4 signaling in injury-induced responses at 1 d, 7 d, and 8 weeks after spinal cord contusion injury in adult female TLR4 null and wild-type mice. Analyses include secondary damage, a range of transcriptome and protein analyses of inflammatory, cell death, and extracellular matrix (ECM) molecules, as well as immune cell infiltration and changes in axonal sprouting and locomotor recovery. Lack of TLR4 signaling results in reduced neuronal and myelin loss, reduced activation of NFκB, and decreased expression of inflammatory cytokines and necroptotic cell death pathway at a late time point (8 weeks) after injury. TLR4 null mice also showed reduction of scar-related ECM molecules at 8 weeks after SCI, accompanied by increase in ECM molecules associated with perineuronal nets, increased sprouting of serotonergic fibers, and improved locomotor recovery. These findings reveal novel effects of TLR4 signaling in chronic SCI. We show that TLR4 influences inflammation, cell death, and ECM deposition at late-stage post-injury when secondary injury processes are normally considered to be over. This highlights the potential for late-stage targeting of TLR4 as a potential therapy for chronic SCI.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismos da Medula Espinal / Citocinas Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismos da Medula Espinal / Citocinas Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá