Neuroglial activation and neuroinflammation in the brain of patients with autism

被引:1512
作者
Vargas, DL
Nascimbene, C
Krishnan, C
Zimmerman, AW
Pardo, CA
机构
[1] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Sch Med, Div Neuroimmunol & Infect Disorders, Baltimore, MD 21287 USA
[3] Univ Milan, Dept Neurol, Milan, Italy
[4] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD USA
[5] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
关键词
D O I
10.1002/ana.20315
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and 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 profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play, a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.
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页码:67 / 81
页数:15
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