Fractionation of spinal cord tissue affects its activity to induce chronic relapsing experimental encephalomyelitis

Chronic relapsing experimental allergic encephalomyelitis (EAE), an animal disease closely resembling multiple sclerosis, was induced in young guinea pigs by sensitization with guinea pig spinal cord tissue together with complete Freund's adjuvant and a high amount of mycobacterium tuberculosis. Sensitization of animals with myelin basic protein leads to an acute form of EAE, but not to a chronic demyelinating disease. The present study was designed to trace the factors of spinal cord tissue responsible for chronic disease and demyelination by using fractionated spinal cord tissue for sensitization. The following preparations were tested for encephalitogenic activity: a) total guinea pig spinal cord homogenized in chloroform/methanol (C/M), b) C/M residue (protein fraction), c) C/M extract (lipid fraction) and d) bovine brain gangliosides. C/M treated spinal cord preparations were less encephalitogenic as compared to untreated spinal cord. The protein fraction showed very little encephalitogenic activity, the histological changes were limited to perivascular inflammation without demyelination. A crude lipid fraction induced some chronic inflammation. Neither the purified lipid fraction nor gangliosides produced any EAE symptoms. The conclusion can be made that protein is necessary for the induction of chronic relapsing EAE, whereas lipid or a protein-lipid complex seems to be responsible for the demyelinating component of this disease.