Experimental autoimmune encephalomyelitis (EAE) has been widely employed as a model to study multiple sclerosis (MS) and indeed has allowed some important advances in our comprehension of MS pathogenesis. Several pieces of evidence suggest that infiltrating Th1 and Th17 lymphocytes are important players leading to CNS demyelination and lesion during the peak of murine EAE. Subsequently, effector T cell responses rapidly decline and the recovery phase of the disease strongly correlates with the expression of anti-inflammatory cytokines and the enrichment of Foxp3+ regulatory T (Treg) cells within the target organ. However, the mechanisms leading to the increased presence of Treg cells and to the remission phase of the disease are still poorly understood. Recent researches demonstrated that chemically induced amino-acid starvation response might suppress CNS immune activity. Here we verified an important participation of the general control nonrepressible 2 (GCN2), a key regulator kinase of the amino-acid starvation response, in the development of the remission phase of EAE in C57BL/6 mice. By immunizing wild type C57BL/6 (WT) and GCN2 knock-out mice (GCN2 KO) with myelin oligodendrocyte glycoprotein peptide (MOG35-55), it was noticed that GCN2 KO mice did not develop the remission phase of the disease and this was associated with higher levels of CNS inflammation and increased presence of effector T cells (Th1/Th17). These animals also showed lower frequency of Treg cells within the CNS as compared to WT animals. Higher expression of indoleamine 2,3-dioxygenase (IDO) and higher frequency of plasmacytoid dendritic cells (pDCs) were found at the peak of the disease in the CNS of WT animals. Our results suggest that the GCN2 kinase-dependent sensing of IDO activity represents an important trigger to the EAE remission phase. The IDO-mediated immunoregulatory events may include the arresting of effector T cell responses and the differentiation/expansion of Treg cells within the target organ.

RESUMO -Lesões desmielinizantes induzidas pelo gliotóxico brometo de etídio (BE) têm sido estudadas com o objetivo de permitir a compreensão do limitado processo de re p a ro mielínico no sistema nerv o s o central, bem como avaliar estratégias terapêuticas no sentido de acelerar a re c o n s t rução das bainhas de mielina perdidas. Muito embora estudos eletrofisiológicos correlacionando situações de desmielinização e remielinização experimental sejam bem estabelecidos, os efeitos comportamentais não têm sido adequadamente investigados. Neste estudo, foram analisadas ultra-estruturalmente as lesões desmielinizantes e a atividade locomotora de ratos submetidos à indução focal de desmielinização pelo modelo do BE na s u p e rfície ventral do tronco encefálico, mediante observação de sua movimentação e controle motor durante a travessia de uma trave elevada de madeira (beam walking test). Foi observada a ocorrência de deficiências locomotoras até 31 dias pós-injeção de BE, constatando-se ainda que a subseqüente remielinização estava relacionada com o retorno da função perdida.PALAVRAS-CHAVE: brometo de etídio, desmielinização, ratos, remielinização, teste da passarela elevada. Evaluation of locomotor activity after a local induction of toxic demyelination in the brainstem of Wistar ratsABSTRACT -Ethidium-bromide (EB) -induced lesions have been used to investigate the incomplete re m y elination in the central nervous system, as well as to evaluate therapeutic strategies to accelerate the re c o n s t ruction of the lost myelin sheaths. Although many electrophysiologic studies were perf o rmed in situations of experimental demyelination and remyelination, their behavioural effects have not been pro p e r l y analyzed. In this study, we investigated ultrastructurally the EB -demyelinating lesions as well as the locomotor activity of rats during the beam walking test after a focal induction of demyelination using the EB model in the ventral surface of the brainstem. It was observed the occurrence of locomotor deficits until 31 days post-injection, as well as that subsequent remyelination was related to the re t u rn of the lost function.KEY WORDS: beam walking test, demyelination, ethidium bromide, rats, remyelination. infiltrantes e de células de Schwann, as últimas acabando por contribuir para o re p a ro mielínico central 8,10 . A remielinização das lesões desmielinizantes tem sido obtida com sucesso através da transplantação de células gliais 1 5 , 1 6 , sugerindo a possibilidade de re p a ro das lesões observadas em doenças como a e s c l e rose múltipla dos seres humanos e a cinomose dos cães com o uso de enxertos de células mielinogê-nicas. No entanto, antes que sua aplicação clínica possa ser contemplada, as conseqüências funcionais da desmielinização e da remielinização espontânea Diversos estudos acerca da desmielinização e da remielinização no sistema nervos central (SNC) têm sido empreendidos baseados no emprego do brometo de etídio (BE), uma droga intercalante gliotóxi-c a 1 -1 4 . Neste modelo, observa-s...

RESUMO -Uma vez que muitos dos aspectos envolvidos na patogenia dos processos desmielinizantes do sistema nervoso central (SNC) são ainda pouco esclarecidos e que os astrócitos parecem estar envolvidos na mediação de tais processos, este estudo analisou morfologicamente a participação astrocitária na desmielinização do SNC por meio da marcação imunoistoquímica de duas proteínas dos filamentos intermediários astrocitários -a proteína glial fibrilar ácida (GFAP) e a vimentina (VIM) -, comparando amostras de cerebelo e de tronco encefálico de oito cães com cinomose e de dois cães normais, de diferentes raças e com idades entre um e quatro anos. Cortes histológicos dos tecidos foram submetidos à marcação pelo método indireto da avidina-biotina-peroxidase (ABC) e a reatividade astrocitária, observada em microscopia de luz, foi quantificada em um sistema computacional de análise de imagens. Observou-se, na maioria dos cortes de animais doentes, a presença de lesões degenerativas compatíveis com desmielinização. A marcação para a GFAP e para a VIM foi mais intensa nos animais com cinomose do que nos animais normais, especialmente nas regiões circunventriculares e nas adjacentes às áreas de degeneração tecidual. Não houve diferença significativa entre a imunomarcação (GFAP e VIM) dos animais com cinomose com e sem infiltração inflamatória da substância branca do cerebelo. O aumento da imunorreatividade dos astrócitos para a GFAP e a reexpressão de VIM nas áreas lesionais indicam o envolvimento astrocitário na resposta do tecido nervoso às lesões desmielinizantes induzidas pelo vírus da cinomose (CDV) no SNC. PALAVRAS-CHAVE: astrócitos, desmielinização do SNC, cinomose canina, GFAP, vimentina. Immunohistochemical staining of the astrocytic expression of glial fibrillary acidic protein and vimentin in the central nervous system of dogs with canine distemper.ABSTRACT -Considering that many aspects involved in the pathogenesis of the central nervous system (CNS) demyelinating diseases are still poorly understood and that astrocytes seem to mediate such processes, this study analyzed the participation of astrocytes in the demyelinating processes of CNS by using immunohistochemical staining of two astrocytic proteins -glial fibrillary acidic protein (GFAP) and vimentin (VIM) -, comparing samples of cerebellum and brainstem from eight dogs with canine distemper and from two healthy dogs, from different breeds and ages varying from 1 to 4 years old. Histological sections were submitted to the avidin-biotin-peroxidase indirect method of immmunohistochemical staining (ABC) and the astrocytic reactivity, observed in light microscopy, was quantified in a computer system for image analysis. It was possible to notice, on most of the sections from sick animals, degenerative lesions that indicate demyelination. The immunostaining for GFAP and VIM was more intense on animals with canine distemper, specially around the ventricules and near degenerated sites. There was no significant difference between the immunostaining (GFAP and VIM) of...

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Despite the lack of information on avian sensitivity to toxic agents, it is known that several products that are relatively harmless to humans may have profound effects on birds. Thus, the objective of this work is to report the case of a plain parakeet (Brotogeris tirica) that was intoxicated after ingesting white glue and to discuss the pathophysiological aspects involved in intoxication. For this, the case study methodology was used, with a qualitative character, describing the case in detail and posteriorly seeking subsidies in the literature centered on the subject under study to complement the knowledge necessary to carry out this study. Twelve hours after ingesting white glue, the plain parakeet (Brotogeris tirica) began to experience recurrent vomiting episodes, which rapidly progressed to a critical condition of dyspnea, prostration and death. Although Polyvinyl Acetate (PVAc), the main component of that type of glue, is described as a non-hazardous substance, necroscopic and histopathological findings, consisting of pulmonary and hepatic congestion and hemorrhage, were very similar to that seen in some avian toxicoses. A thorough review on in vivo and in vitro mechanisms of PVAc degradation suggests that an association of high-dose exposition and B-esterase insufficiency in birds was the probable cause of PVAc poisoning, serving as an alert to veterinarians and bird owners.