Chronic iron overload induces gender-dependent changes in iron homeostasis, lipid peroxidation and clinical course of experimental autoimmune encephalomyelitis.

To analyze iron- and gender-dependent mechanisms possibly involved in pathogenesis of multiple sclerosis (MS) in this study we evaluated the effects of iron overload (IO) on iron status and lipid peroxidation processes (LPO) in tissues of female and male DA rats during chronic relapsing experimental autoimmune encephalomyelitis, a well-established MS animal model. Rats were treated by iron sucrose (75mg/kg bw/day) or with saline solution during two weeks before the sensitization with bovine brain homogenate in complete Freund's adjuvant. Clinical signs of EAE were monitored during 29 days. Serum and tissues of CNS and liver were sampled before immunization and at day 13th post immunization (during acute phase of EAE). The determination of ferritin, iron, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and evaluation of histopathology were performed by ELISA, ICP spectrometry and immunohistochemistry. Results showed that IO in female EAE rats accelerated the onset of disease. In contrast, in male rats it accelerated the progression of disease and increased the mortality rate. During acute phase of EAE female IO rats sequestered more Fe in the liver, spinal cord and in the brain and produced more ferritin than male EAE rats. Male rats, however, reacted on IO by higher production of MDA or 4-HNE in the neural tissues and showed greater signs of plaque formation and gliosis in spinal cord. The data point to sexual dimorphism in mechanisms that regulate peripheral and brain iron homeostasis and imply that men and women during MS might be differentially vulnerable to exogenous iron overload.

Ameliorating effects of hyperbaric oxygenation on experimental allergic encephalomyelitis.

The effect of hyperbaric oxygenation (OHP) on survival and quality of survival of guinea pigs afflicted with experimental allergic encephalomyelitis (EAE) was investigated. EAE was induced in Hartley and Strain 13 animals by intradermal injections of whole guinea pig spinal cord in complete Freund's adjuvant. The inoculated animals were divided into control and treatment groups; the treated animals received OHP in a variety of treatment schedules. Clinical signs of EAE were quantitated and mean survival times were measured. When Hartley animals were exposed to 100% O2 at 2.5 atmospheres absolute (ATA) for 2 hr/day from 5--19 days postinoculation, the mean survival time (+/- SE) was 19.1 +/- 1.6 days relative to 15.7 +/- 0.7 days in the control (p less than 0.050). When Strain 13 guinea pigs were treated with 100% O2 at 2ATA for 4 hr/day on 5--16 days, the mean survival time was 21.6 +/- 0.6 days compared to 16.0 +/- 0.4 days for the control (p less than 0.001). Clinical sign measurements demonstrated that the onset of EAE in the treated animals of both strains occurred between 4--6 days after these signs became detectable in control animals. These results suggest that OHP therapy can ameliorate EAE in afflicted guinea pigs.

Enhancement of encephalitogenic activity by the formation of myelin basic protein-brain acidic protein complex.

Encephalitogenic protein fraction (BEC) was isolated from bovine brain tissue by extraction with salt-ethanol mixture at neutral pH, instead of employing dilute mineral acid. The fraction BEC was separated into two fractions. An acid-soluble protein was encephalitogenic and the major component was very alike to the basic protein of myelin (Al). The other was acid-insoluble acidic protein that was not encephalitogenic even at a dose of 100 mug. The acidic protein formed an insoluble complex with Al rotein which was purified by Eylar's method. Encephalitogenic activity of the complex was higher than Al protein in young guinea pigs when injected with complete Freund's adjuvant.However, this enhancement of encephalitogenic activity was not observed in aged guinea pigs. The complex showed higher blastogenic activity than Al protein alone with peripheral blood lymphocytes from guinea pigs immunized with Al protein and complete Freund's adjuvant. These results show that an adjuvant-like acidic protein is present in brain tissue and the complex with Al protein enhances the induction of experimental allergic encephalomyelitis (EAE).