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Substantial evidence indicates that stress can precipitate or worsen symptoms of inflammation in general and more specifically in multiple sclerosis (MS), a demyelinating, autoimmune disease characterized by inflammation of the central nervous system (CNS). However, the mechanism of how stress affects MS is not well understood. We reviewed publications in PubMed since 1995 and propose that neuropeptides secreted under stress, such as corticotropin releasing hormone (CRH) and neurotensin (NT), activate microglia and mast cells to release inflammatory molecules. These lead to maturation and activation of T17 autoimmune cells, disruption of the blood–brain barrier (BBB) and T cell entry into the CNS, thus promoting brain inflammation and contributing to MS pathology. Reduction of stress and inhibition of these processes by select flavonoids could provide novel therapeutic approaches.

Our study suggests that a four-week diet rich in either palmitic acid or linoleic acid induces an oxidative stress in the rat liver of non-diabetic rats, as shown by increased lev- els of hepatic TBARS and changes in the activity of antiox- idant enzymes. Therefore, in healthy subjects high content in a diet of both saturated (palmitic) and polyunsaturated (linoleic) fatty acids should be considered a potentially harmful factor with respect to pro- and antioxidative bal- ance in the liver. However, in diabetic rats a diet rich in linoleic acid partially prevents STZ-induced generation of peroxidation products, thus it appears to attenuate the oxidative stress in the liver. A diet rich in palmitic acid does not seem to modify diabetes-induced oxidative stress effec- tively, since it does not change the level of TBARS, despite significant diet-induced changes in antioxidant enzyme activity.

Whether PUFA diets affect inflammatory mediators in central and peripheral sites is not clear. We investigated the effect of high-fat PUFA diets on the expression of proteins involved in inflammatory pathways in hypothalamus, muscle, and liver. Male rats were fed for 2 months with either chow or high-fat diets enriched with either soy (n-6 PUFAs) or fish oil (n-3 PUFAs). The fish group had normal body weight, low serum NEFA, reduced hypothalamic levels of TNF-α, IL-6, and TRAF6, and increased levels of IL-10 receptor. In contrast, the soy group had increased body weight and hypothalamic levels of TRAF6 and NFκBp65. In muscle, the fish diet reduced TNF-α and IL-6 levels. Both PUFA diets increased muscle IL-10 levels and reduced liver TNF-α and IL-6 levels. The data showed that the high-fat soy diet induced activation of the hypothalamic NFκB inflammatory pathway, a feature predisposing to feeding and energy expenditure disturbances associated with the development of obesity. On the other hand, the high-fat fish diet improved the central and the peripheral inflammatory profile via reduction of intracellular inflammatory mediators, suggesting a protection against obesity.

Dysfunction of the blood–brain barrier (BBB) is an early pathological feature of vascular dementia and Alzheimer's disease (AD) and is triggered by inflammatory stimuli. Probucol is a lipid-lowering agent with potent anti-oxidant properties once commonly used for the treatment of cardiovascular disease. Probucol therapy was found to stabilize cognitive symptoms in elderly AD patients, whereas in amyloid transgenic mice probucol was shown to attenuate amyloidosis. However, the mechanisms underlying the effects of probucol have note been determined.
In the present study we investigated whether probucol can prevent BBB disturbances induced by chronic ingestion of proinflammatory diets enriched with either 20% (w/w) saturated fats (SFA) or 1% (w/w) cholesterol. Mice were fed the diets for 12 weeks before they were killed and BBB integrity was measured.
Mice maintained on either the SFA- or cholesterol-supplemented diets were found to have a 30- and sevenfold greater likelihood of BBB dysfunction, respectively, as determined by the parenchymal extravasation of plasma-derived immunoglobulins and endogenous lipoprotein enrichment with β-amyloid. In contrast, mice fed the SFA- or cholesterol-enriched diets that also contained 1% (w/w) probucol showed no evidence of BBB disturbance. The parenchymal expression of glial fibrillary acidic protein, a marker of cerebrovascular inflammation, was significantly greater in mice fed the SFA-enriched diet. Plasma lipid, β-amyloid and apolipoprotein B levels were not increased by feeding of the SFA- or cholesterol-enriched diets. However, mice fed the SFA- or cholesterol-enriched diets did exhibit increased plasma non-esterified fatty acid levels that were not reduced by probucol.
The data suggest that probucol prevents disturbances of BBB induced by chronic ingestion of diets enriched in SFA or cholesterol by suppressing inflammatory pathways rather than by modulating plasma lipid homeostasis.