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CNS Neurosci Ther ; 23(9): 724-735, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28718218

RESUMO

AIM: Brain inflammation is associated with several brain diseases such as multiple sclerosis (MS), a disease characterized by demyelination. Whether prenatal immune challenge affects demyelination-induced inflammation in the white matter during adulthood is unclear. In the present study, we used a well-established experimental model of focal demyelination to assess whether prenatal immune challenge affects demyelination-induced inflammation. METHODS: Pregnant rats were injected with either lipopolysaccharide (100 µg/kg, ip) or pyrogen-free saline. A 2 µL solution of the gliotoxin ethidium bromide (0.04%) was stereotaxically infused into the corpus callosum of adult male offspring. The extent of demyelination lesion was assessed using Luxol fast blue (LFB) staining. Oligodendrocyte precursor cells, mature oligodendrocytes, markers of cellular gliosis, and inflammation were monitored in the vicinity of the demyelination lesion area. RESULTS: Prenatal lipopolysaccharide reduced the size of the demyelination lesion during adulthood. This reduced lesion was associated with enhanced density of mature oligodendrocytes and reduced density of microglial cells in the vicinity of the demyelination lesion. Such reduction in microglial cell density was accompanied by a reduced activation of the nuclear factor κB signaling pathway. CONCLUSION: These data strongly suggest that prenatal immune challenge dampens the extent of demyelination during adulthood likely by reprogramming the local brain inflammatory response to demyelinating insults.


Assuntos
Doenças Desmielinizantes/etiologia , Bainha de Mielina/patologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Animais Recém-Nascidos , Proteínas de Ligação ao Cálcio/metabolismo , Citratos/toxicidade , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/patologia , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Feminino , Gliotoxina/análogos & derivados , Gliotoxina/toxicidade , Imunossupressores/toxicidade , Lipopolissacarídeos/toxicidade , Masculino , Proteínas dos Microfilamentos/metabolismo , Proteínas da Mielina/metabolismo , Bainha de Mielina/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
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