Generating the Widespread Cerebral Cortical Demyelination in a Rat Model

Begin with an emulsion of recombinant myelin sheath protein with an adjuvant.

Inject this mixture into the subcutaneous layer at the tail of an anesthetized rat, which has a pre-positioned catheter in the brain.

The adjuvant enhances immune responses to antigens in the subcutaneous layer and lymph nodes, generating effector T cells that enter the circulation.

Using the pre-implanted catheter, administer pro-inflammatory cytokines directly into the brain.

These cytokines spread in the cerebral cortex and disrupt the endothelial cell junctions in the blood vessels.

This allows the entry of various immune cells into the cerebral cortex.

Monocytes differentiate into macrophages, releasing reactive oxygen species that cause myelin sheath-producing oligodendrocyte death.

B cells interact with effector T cells, differentiating the B cells that secrete antibodies against myelin sheath protein.

These antibodies interact with myelin sheath protein, damaging the myelin sheath around the neurons.

This results in widespread cerebral cortical demyelination in a rat model.