Pathomechanisms of anti-NMDA receptor encephalitis

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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.