cqvip:Autism is a neurodevelopmental disorder characterized by impaired communicati on and social interaction and may be accompanied by mental retardation and epile psy. Its cause remains unknown, despite evidence that genetic, environmental, an d immunological factors may play a role in its pathogenesis. To investigate whet her immune mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme linked immunosor bent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic p atients and determined the magnitude of neuroglial and inflammatory reactions an d their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profili ng. We demonstrate an active neuroinflammatory process in the cerebral cortex, w hite matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profil ing indicated that macrophage chemoattractant protein (MCP) 1 and tumor growth factor β 1, derived from neuroglia, were the most prevalent cytokines in bra in tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP 1. Our findings indicate that innate neuroimmune reac tions play a pathogenic role in an undefined proportion of autistic patients, su ggesting that future therapies might involve modifying neuroglial responses in t he brain.
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