Valproic acid attenuates inflammation in experimental autoimmune neuritis

Valproic acid (VPA) is a short-chain branched fatty with anti-inflammatory, neuro-protective and axon-remodeling effects. We investigated the effects of VPA in rats in which experimental autoimmune neuritis (EAN) had been induced (EAN rats). VPA (300 mg/kg, intraperitoneally) administration to EAN rats once daily immediately following immunization significantly suppressed mRNA levels of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6 and IL-17 in the lymph nodes of EAN rats. In peripheral blood and sciatic nerves of EAN rats, Foxp3⁺ cells were increased but IL-17⁺ cells were decreased during VPA treatment. Furthermore, suppressive and therapeutic treatment with VPA greatly attenuated both accumulation of macrophages, T cells and B cells, and demyelination in sciatic nerves, and greatly reduced the severity and duration of EAN. In summary, our data demonstrated that VPA could effectively suppress inflammation in EAN, suggesting that VPA could be a potent candidate for treatment of autoimmune neuropathies.     

Low-molecular-weight enzyme inhibitors suppress the development of experimental allergic encephalomyelitis

Summary We tested the activity of low-molecular-weight enzyme inhibitors with immunomodifying actions on the suppression of experimental allergic encephalomyelitis (EAE). Of the agents tested the inhibitors of alkaline phosphatase, aminopeptidase B and esterase gave significant protection againts the clinical expression of EAE in guinea pigs.Acknowledgments. This work was partly supported by a grant-in-aid for New Drug Development Research from the Ministry of Health and Welfare, Japan.     

Low-molecular-weight enzyme inhibitors suppress the development of experimental allergic encephalomyelitis

We tested the activity of low-molecular-weight enzyme inhibitors with immunomodifying actions on the suppression of experimental allergic encephalomyelitis (EAE). Of the agents tested the inhibitors of alkaline phosphatase, aminopeptidase B and esterase gave significant protection against the clinical expression of EAE in guinea pigs.     

Agglutinating antibrain antibodies in dogs with experimental allergic encephalomyelitis

Résumé Chez 19 chiens présentant des symptomes de EAE, on a trouvé des anticorps sériques anticerveaux pendant divers laps de temps.     

Suppression of experimental allergic encephalomyelitis by vitamin A

Résumé L'encéphalomyélite allergique expérimentale n'apparaît pas chez les cobayes auxquels on a injecté de fortes doses de vitamine A.

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The authors are indebted toElisabeth Móre for technical assistance.     

Effect of experimental allergic encephalomyelitis γ-globulin upon the electrical activity of the brain

Zusammenfassung Die direkte Wirkung eines-Globulin-Präparates aus Kaninchenserum (Injektion in laterale Hirnkammer des Kaninchens) auf die experimentelle allergische Encephylomyelitis wurde dargestellt und elektroencephalographisch eine Inaktivierung verschiedener Hirnregionen festgestellt.     

Effect of blood pH on anionic ferritin transport through rat aortic endothelium

Summary Acute lowering of blood pH between 7.4 and 6.9 in rats by ventilation with 10 or 20% CO₂ does not increase the passage of ferritin molecules across the aortic endothelium. These results do not rule out alteration of endothelial permeability to anionic macromolecules in local circulatory disturbances when blood pH drops to levels much lower than 6.9.Supported by The Medical Research Council of Canada grant No. MA-5958.Dr J.R. Fraser was a recipient of a Summer Research Scholarship from McGill University during the completion of this study.The authors thank Colin Bier for the statistical analysis.     

Effect of blood pH on anionic ferritin transport through rat aortic endothelium.

Acute lowering of blood pH between 7.4 and 6.9 in rats by ventilation with 10 or 20% CO2 does not increase the passage of ferritin molecules across the aortic endothelium. These results do not rule out alteration of endothelial permeability to anionic macromolecules in local circulatory disturbances when blood pH drops to levels much lower than 6.9.     

Decrease in motor activity - an early symptom in the course of experimental allergic encephalomyelitis (EAE).

Motor activity has been followed in rats during an experimental allergic encephalomyelitis (EAE). The disease was produced by transfer of lymph node cells from sensitized syngenic donors. Small and large movements were permanently registered by an electric activity meter. It could be demonstrated that a decrease of the motility is an early symptome of the disease. Therefore the measurement of the motoric activity might be a useful parameter in the classification of EAE.     

Decrease in motor activity — an early symptom in the course of experimental allergic encephalomyelitis (EAE)

Summary Motor activity has been followed in rats during an experimental allergic encephalomyelitis (EAE). The disease was produced by transfer of lymph node cells from sensitized syngenic donors. Small and large movements were permanently registered by an electric activity meter. It could be demonstrated that a decrease of the motility is an early symptome of the disease. Therefore the measurement of the motoric activity might be a useful parameter in the classification of EAE.To whom reprint requests should be addressed.Acknowledgments. We thank ABFARAD Nyborgsgränd 1, 12634 Hägersten (Sweden) for making the Animex activity meter available to us. The experiments were supported by the Deutsche Forschungsgemeinschaft.     

On the mechanism of the involvement of endothelium in reactive hyperemia

Experiments on anesthetized dogs and on vascular test-preparations demonstrated that reactive hyperemia (RH) was accompanied by the appearance of vasodilator in the blood, and that the level increased with the duration of occlusion of the artery. Removal of the endothelium of the part of the vascular bed studied using saponin, decreased the RH and relaxation of a test-preparation. A rise of pressure in the vascular bed, and a decrease in the deformability of the endothelium resulting from pretreatment with dimerized glutaraldehyde, affected both the hyperemia and the reaction of the vascular preparation in a similar way. It was concluded that the RH resulted from the secretion of vasoactive substances by the endothelium in response to a fall in intravascular pressure.     

Antigen-specific T cells in autoimmune diseases with a focus on multiple sclerosis and experimental allergic encephalomyelitis

Although the pathogenesis of autoimmune diseases remains poorly understood, the current view is that autoaggresive antigen-specific T cells play a central role in the cascade of events leading to most autoimmune diseases. A major event in the development of autoimmune diseases is the activation of antigen-specific T cells-how, when and where does this activation take place? This review addresses questions concerning the occurrence of unique autoantigens triggering autoimmune diseases, the factors influencing the balance between self-tolerance and autoaggresive immunity, and the mechanisms by which dendritic cells mediate immunity and tolerance to antigen-specific T cells. Knowledge of how antigen-specific T cells are activated is now being used to develop therapeutic approaches to control autoimmune diseases. We discuss tolerance to antigen-specific T cells and tolerance induction as treatment of T-cell-mediated autoimmune diseases. Therapeutic modalities have been established which selectively target the pathogenic T cells. leaving the remainder of the immune system intact.     

On the mechanism of the involvement of endothelium in reactive hyperemia

Experiments on anesthetized dogs and on vascular test-preparations demonstrated that reactive hyperemia (RH) was accompanied by the appearance of vasodilator in the blood, and that the level increased with the duration of occlusion of the artery. Removal of the endothelium of the part of the vascular bed studied using saponin, decreased the RH and relaxation of a test-preparation. A rise of pressure in the vascular bed, and a decrease in the deformability of the endothelium resulting from pretreatment with dimerized glutaraldehyde, affected both the hyperemia and the reaction of the vascular preparation in a similar way. It was concluded that the RH resulted from the secretion of vasoactive substances by the endothelium in response to a fall in intravascular pressure.     

Cellular membrane activity in the corneal endothelium of the intact eye

Zusammenfassung Die direkte Beobachtung des Hornhautendothels wird mit einem speziellen Mikroskop möglich. Formveränderungen der Zellen, besonders ihrer Oberflächenmembranen, lassen sich zeigen.