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Overcoming Unresponsiveness in Experimental Autoimmune Encephalomyelitis (EAE) Resistant Mouse Strains by Adoptive Transfer and Antigenic Challenge
Published on: April 9, 2012
Amelioration of experimental allergic encephalitis (EAE) through phase 2 enzyme induction
A A Mohamed1, J G Avila, E Schültke
1Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada.
Abstract:
The multiple sclerosis (MS) lesion is characterized by an inflammatory cell mediated attack on white matter. Oxidative stress appears to play a role in the onset and progression of MS. We reasoned that decreasing oxidative stress might ameliorate MS. One way of decreasing oxidative stress is to induce phase 2 enzymes. The model chosen to test this hypothesis was experimental allergenic encephalomyelitis (EAE) induced in the Lewis rat. The 26 animals were placed into two groups: 1) those on normal rat chow, 2) those on rat chow containing 250 mumoles t-butylhydroxyanisole (BHA)/kg. After 2 weeks, animals were administered 100 micrograms guinea pig myelin basic protein and examined daily in a blinded fashion. Twenty-nine days later, animals were sacrificed, blood collected for glutathione (GSH) measurements and tissues collected for histology. Six of the 13 control chow animals developed hindlimb weakness or paralysis while 5 developed tail weakness only. Only 1 BHA fed animal exhibited symptoms--hindlimb weakness. Clinical symptoms correlated well with the extent of perivascular lymphocyte infiltration. Animals with BHA in the diet had 20% higher red cell GSH indicting induction of phase 2 enzymes. We conclude that dietary phase 2 enzyme inducers should be examined for their ability to ameliorate MS.
Insights
Dietary phase 2 enzyme inducers, like BHA, show promise in reducing oxidative stress and ameliorating multiple sclerosis (MS) symptoms in rats. This suggests a potential new therapeutic avenue for MS treatment.
Area of Science:
- Neuroimmunology
- Biochemistry
- Toxicology
Background:
- Multiple sclerosis (MS) involves inflammatory attacks on white matter, with oxidative stress contributing to disease progression.
- Inducing phase 2 enzymes is a strategy to decrease oxidative stress.
- Experimental autoimmune encephalomyelitis (EAE) in Lewis rats serves as a model for MS.
Purpose of the Study:
- To investigate whether decreasing oxidative stress by inducing phase 2 enzymes can ameliorate MS.
- To evaluate the effect of dietary t-butylhydroxyanisole (BHA) on EAE symptoms and oxidative stress markers.
Main Methods:
- EAE was induced in Lewis rats, divided into control and BHA-supplemented diet groups.
- Animals were monitored daily for clinical symptoms, and blood and tissues were collected for analysis.
- Red blood cell glutathione (GSH) levels were measured to assess phase 2 enzyme induction.
Main Results:
- Rats fed BHA exhibited significantly reduced clinical symptoms compared to controls.
- BHA-fed animals showed a 20% increase in red blood cell GSH, indicating successful phase 2 enzyme induction.
- Histological analysis revealed a correlation between reduced clinical symptoms and decreased perivascular lymphocyte infiltration.
Conclusions:
- Dietary induction of phase 2 enzymes, demonstrated by BHA, can ameliorate EAE, a model for MS.
- Reducing oxidative stress through dietary interventions may be a viable strategy for managing MS.
- Further research into dietary phase 2 enzyme inducers for MS treatment is warranted.
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