Pardo Carlos A, Vargas Diana L, Zimmerman Andrew W
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Int Rev Psychiatry. 2005 Dec;17(6):485-95. doi: 10.1080/02646830500381930.
Autism is a complex neurodevelopmental disorder of early onset that is highly variable in its clinical presentation. Although the causes of autism in most patients remain unknown, several lines of research support the view that both genetic and environmental factors influence the development of abnormal cortical circuitry that underlies autistic cognitive processes and behaviors. The role of the immune system in the development of autism is controversial. Several studies showing peripheral immune abnormalities support immune hypotheses, however until recently there have been no immune findings in the CNS. We recently demonstrated the presence of neuroglial and innate neuroimmune system activation in brain tissue and cerebrospinal fluid of patients with autism, findings that support the view that neuroimmune abnormalities occur in the brain of autistic patients and may contribute to the diversity of the autistic phenotypes. The role of neuroglial activation and neuroinflammation are still uncertain but could be critical in maintaining, if not also in initiating, some of the CNS abnormalities present in autism. A better understanding of the role of neuroinflammation in the pathogenesis of autism may have important clinical and therapeutic implications.
自闭症是一种起病较早的复杂神经发育障碍,其临床表现具有高度变异性。尽管大多数自闭症患者的病因尚不清楚,但多项研究支持这样的观点,即遗传和环境因素都会影响异常皮质神经回路的发育,而这种异常神经回路是自闭症认知过程和行为的基础。免疫系统在自闭症发展过程中的作用存在争议。多项研究显示外周免疫异常,这支持了免疫假说,然而直到最近,中枢神经系统中都没有免疫相关的发现。我们最近在自闭症患者的脑组织和脑脊液中证实了神经胶质细胞和先天性神经免疫系统的激活,这些发现支持了这样一种观点,即自闭症患者大脑中存在神经免疫异常,这可能导致自闭症表型的多样性。神经胶质细胞激活和神经炎症的作用仍不确定,但即使不是引发,也可能对维持自闭症患者中枢神经系统中存在的一些异常情况至关重要。更好地理解神经炎症在自闭症发病机制中的作用可能具有重要的临床和治疗意义。