Co-Administration of LPC and LPS Enhanced the Spinal Cord Vulnerability in a Mouse Model of Focal Demyelination

Focal demyelination refers to localized loss of myelin sheath that surrounds the nerve fibers. It impairs the efficient transmission of nerve impulses results in neurological symptoms. Here, our goal is to investigate the differential and combined effects of lysolecithin (LPC) and lipopolysaccharides (LPS) on brain and spinal cord demyelinating process. To confirm the pattern of demyelination, behavioural analysis was performed. Further, brain and spinal cord samples were collected at Day-post injection-1, 3, 7, and 28. The loss of axonal structures and neuronal bodies were assessed using Luxol fast blue and Nissl staining respectively. Immunofluorescence studies were done to examine demyelination and its impact on endothelial activation, astrogliosis, and activated microglia. Our data revealed that the combination group exhibited remarkable demyelination compared to the LPC and LPS groups alone. Additionally, endothelial activation, astrogliosis, and activated microglia were more pronounced in the combination group. Moreover, we found much of these effects were most pronounced in the spinal cord compared to corpus callosum, suggesting the presence of compensatory mechanisms and a unique brain microenvironment. This study is the first to demonstrate the synergistic effects of LPC and LPS toxins compared to their individual effects in both the brain and spinal cord.