Tlr4 Deletion Modulates Cytokine and Extracellular Matrix Expression in Chronic Spinal Cord Injury, Leading to Improved Secondary Damage and Functional Recovery

Spinal cord injury (SCI) often results in permanent loss of motor and sensory function. This study investigates the role of Toll-like receptor 4 (TLR4), a protein involved in the immune response, in the chronic phase after SCI. The research shows that deleting the TLR4 gene in mice leads to reduced inflammation, cell death, and scar tissue formation in the spinal cord months after the initial injury. These changes are associated with improved nerve fiber sprouting and locomotor recovery, suggesting that targeting TLR4 could be a potential therapy for chronic SCI.

• 1
  TLR4 deletion reduces neuronal and myelin loss, decreasing secondary damage at 8 weeks post-SCI.
• 2
  TLR4 null mice exhibit reduced activation of NFκB and decreased expression of inflammatory cytokines and the necroptotic cell death pathway at 8 weeks post-injury.
• 3
  TLR4 deletion leads to a reduction in scar-related ECM molecules and increased ECM molecules associated with perineuronal nets, enhancing serotonergic fiber sprouting and locomotor recovery.