Regional Vulnerability to Demyelination: A Comparative Study of the Effects of LPC, LPS, and Combined Toxins in Corpus Callosum and Spinal Cord

Focal demyelination refers to localized loss of myelin sheath surrounds the nerve fibers. It impairs the efficient transmission of nerve impulses results in neurological symptoms. Our goal is to investigate the differential effects of lysolecithin (LPC) and lipopolysaccharides (LPS) on demyelinating processes of central nervous system. We established a novel demyelinating model using a combination of LPC and LPS with their differential effects in the corpus callosum of brain and the thoracic region of the spinal cord. 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 extent of demyelination and the presence of Nissl ⁺ cells were assessed using Luxol fast blue and Nissl staining respectively. Immunofluorescence studies were done to examine demyelination and its impact on endothelial cells dysfunction, astrogliosis, and activated microglia. Our data revealed that the combination group exhibited remarkable demyelination compared to the LPC and LPS groups alone. Additionally, vascular dysfunction, astrogliosis, and activated microglia were more pronounced in the combination group. Moreover, we found much of these effects were most promising 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 integrated effects of LPC and LPS toxins compared to their individual effects in both the brain and spinal cord.