Pathomechanisms of anti-NMDA receptor encephalitis

为探讨抗N-甲基-D-天冬氨酸受体(NMDAR)抗体对NMDAR脑炎患者神经症状的影响。NMDAR脑炎的主要症状是健忘症，以及抽搐和其他精神症状。为了再现这些症状，我们检查了长期接触患者脑脊液(CSF)的小鼠的行为，发现注射了脑脊液的小鼠表现出学习障碍。然而，他们的脑组织没有表现出炎性细胞浸润、神经元丢失或神经胶质细胞增殖，也没有炎性细胞因子的增加。因此，我们首次发现NMDAR脑炎患者的脑脊液直接干扰了小鼠的记忆功能。这些影响被认为是功能性的，没有神经组织破坏，这与这种疾病的良好结局是一致的。

The roles of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies from patients with NMDAR encephalitis on their neurological symptom were examined. The major symptom of NMDAR encephalitis is known as amnesia together with convulsions and other psychiatric symptoms. To reproduce these symptoms, we examined behavior of mice exposed chronically to the cerebrospinal fluid (CSF) from patients and found that mice injected with the CSF exhibited learning impairment. However, their brain tissues did not exhibit inflammatory cell infiltration, neuronal loss, or glial proliferation, and there was no increase in inflammatory cytokines. Thus, for the first time, we showed that the CSF from NMDAR encephalitis patients disturbed the memory function directly in mice. These effects were considered to be functional and without neuronal tissue destruction, which is compatible with the favorable outcome of this disease.