Relaxin-2 Ameliorates Spinal Cord Injury by Inhibiting Microglia Activation.

Abstract

This study aims to assess the therapeutic effectiveness of Relaxin-2 (RLN-2) in promoting functional recovery and neuroprotection following spinal cord injury (SCI) in mice. Furthermore, continuous subcutaneous infusion of Serelaxin (0.5 mg/kg/day; human recombinant relaxin-2) improved neurological recovery, as evidenced by higher Basso-Beattie-Bresnahan (BBB) scores and reduced foot-stepping angles compared to the SCI group. Additionally, RLN-2 effectively reduced edema in the injured spinal cord, as shown by decreased water content and downregulated AQP4 expression at mRNA and protein levels. RLN-2 reduced oxidative stress markers such as malondialdehyde (MDA) and reactive oxygen species (ROS) and increased the activity of catalase (CAT). Further, RLN-2 mitigated neuroinflammation by reducing the levels of pro-inflammatory cytokines (TNF-α and IL-6) and by inhibiting the activation of M1 microglia while promoting the polarization of M2 microglia. It also inhibited the activation of the NF-κB signaling and strengthened the activation of the STAT6 signaling in the spinal cord of SCI mice. These findings suggest that RLN-2 may be a promising therapeutic agent for the treatment of spinal cord injury.