Schwann cell transplantation exerts neuroprotective roles in rat model of spinal cord injury by combating inflammasome activation and improving motor recovery and remyelination

Abstract

Inflammasome activation in the traumatic central nervous system (CNS) injuries is responsible for propagation of an inflammatory circuit and neuronal cell death resulting in sensory/motor deficiencies. NLRP1 and NLRP3 are known as activators of inflammasome complex in the spinal cord injury (SCI). In this study, cell therapy using Schwann cells (SCs) was applied for targeting NLRP inflammasome complexes outcomes in the motor recovery. These cells were chosen due to their regenerative roles for CNS injuries. SCs were isolated from sciatic nerves and transplanted to the contusive SCI-induced Wistar rats. NLRP1 and NLRP3 inflammasome complexes and their related pro-inflammatory cytokines were assayed in both mRNA and protein levels. Neuronal cell survival (Nissl staining), motor recovery and myelination (Luxol fast blue/LFB) were also evaluated. The groups were laminectomy, SCI, vehicle and treatment. The treatment group received Schwann cells, and the vehicle group received solvent for the cells. SCI caused increased expressions for both NLRP1 and NLRP3 inflammasome complexes along with their related pro-inflammatory cytokines, all of which were abrogated after administration of SCs (except for IL-18 protein showing no change to the cell therapy). Motor deficits in the hind limb, neuronal cell death and demyelination were also found in the SCI group, which were counteracted in the treatment group. From our findings we conclude promising role for cell therapy with SCs for targeting axonal demyelination and degeneration possibly through attenuation of the activity for inflammasome complexes and related inflammatory circuit.

Keywords: Inflammation; NLRP; Schwann cells; Spinal cord injury (SCI).