DNA changes in spinal cords of rats with experimental allergic encephalomyelitis.
DNA levels were measured in the spinal cords of Lewis rats during the development of and recovery from experimental allergic encephalomyelitis (EAE). Spinal cord DNA was first increased 11 days after immunizing the rats with guinea pig myelin and rose to levels four times that of the Freund's adjuvant controls at day 14, then subsided after day 22. Spinal cord DNA was still 150% of control levels 60 days after immunization. These DNA changes were compared with fluctuations in spinal cord acid proteinase in the same animals. Acid proteinase activity in EAE spinal cord increased later than the rise in DNA and attained a level of 170% of control at days 15-17, then subsided. Spinal cord DNA was higher in rats immunized with whole myelin than in those administered equivalent amounts of purified myelin basic protein. Furthermore DNA was higher in spinal cords of rats immunized with a larger dose of myelin (1.0 mg) than with a lower amount (0.5 mg). Various protease inhibitors including pepstatin, nitrophenyl p-guanidino benzoate, polylysine, and dipropionyl rhein, previously shown to protect Lewis rats against EAE, suppressed the increase of DNA in the spinal cord. Measurement of DNA increases in the spinal cord of EAE animals provides a convenient reproducible measurement of the severity of inflammation in the CNS and provides an objective criterion for assessment of the efficacy of various agents screened as possible therapeutic treatment for multiple sclerosis.
D000818:Animals; D016282:Aspartic Acid Endopeptidases; D004247:DNA / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006168:Guinea Pigs; D007114:Immunization; D007700:Kinetics; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D004676:Myelin Basic Protein; D011480:Protease Inhibitors; D004247:DNA; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases