Acute systemic single injection of Lipopolysaccharide mediated local polarization of macrophage/microglia phenotype and functional recovery following contusion spinal cord injury

Background and Aim : mechanical impact on the spinal cord disturbs ascending and descending tracts at the level of injury, resulting in loss of sensation and motor control respectively. Moreover, secondary cascade exuberated spinal milieu and damage propagates to the rostral and caudal of the lesion site. Post-traumatic SCI inflammation is a persistent feature of the spinal cord microenvironment. phenotype diversity of macrophages/microglia (M1/M2) exists in the injured spinal cord and this heterogeneity may responsible for dual detrimental or beneficial roles of inflammation in regulating regenerative capacity. The aim of the present study was to evaluate the possible effect of early activation of TLR4 signaling via their ligand: LPS, after contusion spinal cord injury model in rats.Methods : We designed a customized impact device to develop Contusion spinal cord injury in rats. Wistar rats, 250-270 g in weight were divided into 5 groups. LPS were intraperitoneally administrated at immediate(2h) or early(6h) time separately at the low doses 0.2 and 0.5 mg/kg. In the present study, we evaluated the expression of pro-inflammatory (CD86, IL-1b, IL-12, NF-kB) and anti-inflammatory (CD206, IL-13, IL-10, C/EBPb) associated gene by quantitative PCR at different time course up to 28 days. We determine the effectiveness of LPS injection in structural remodeling and behavioral outcomes after SCI.Results : First, we have found that SCI induces a temporal change in inflammatory marker up to 4 weeks. LPS administration could modulate local inflammation and LPS 0.5 mg/kg acutely reduces the mRNA level of pro-inflammatory M1 at least for 24h post-SCI. functional analysis demonstrated that all treatment groups with LPS showed improvement in spontaneous motor recovery in a dose-dependent manner compared to the SCI group. it was observed that the evaluated score of the BBB was higher in rats received LPS 0.5 mg/kg at an early (6h) phase compare to other groups for 4 weeks. And also, early (6h) treatment with LPS 0.5 mg/kg reduces lesion site.Conclusion : Importantly, systemic LPS administration displayed a local anti-inflammatory beneficial role, through a shift in the polarization of macrophage is associated with improved tissue sparing and functional recovery which may contribute to the reduction in the expression ratio of CD86/CD206.

کلیدواژه ها:

spinal cord injury ، macrophage polarization ، inflammation ، motor recovery