Abstract
OBJECTIVE: To analyze the role of C5a, C5a receptor (CD88), glutamic acid, and N-methyl-D-aspartic acid receptors (NMDAR1 and NMDAR2B) in the onset of neuromyelitis optica (NMO) disease in mice. METHOD: To select C57BL/6 wild-type (WT) mice and C5a receptor gene knockout (C5aR-/-) mice, use NMO-IgG and hemolytic complement to intervene in spinal cord tissue sections and optic nerves to establish an NMO model in vitro. The experiment was carried out with five groups (control group, WT group, C5aR-/- group, C5a group, and C5a+C5aRA group), with six mice in each group. The differences of American spinal cord injury (ASIA) motor scores were compared among all groups. The expressions of aquaporin (AQP4), glial fibrillary acidic protein (GFAP), NMDAR1, and NMDAR2B in spinal cord and optic nerve tissues were detected. The difference of glutamic acid (Glu) concentrations in culture solutions of the spinal cord and optic nerves was compared. RESULT: The ASIA motor score of the control group was significantly lower than that of the other four groups. The C5a-/- group was significantly higher than the WT group. The C5a+C5aRA group was significantly higher than the C5a group in terms of ASIA motor score. In the control group, AQP4 and GFAP showed expression loss. The C5aR-/- group's loss rate was significantly higher than that of the WT group. The loss rate of the C5a+C5aRA group was significantly higher than that of the C5a group. In the control group, the protein expressions of NMDAR1 and NMDAR2B were significantly lower than that of the other four groups. The C5aR-/- group was significantly higher than the WT group. The C5a+C5aRA group was significantly higher than the C5a group in protein expression. In the control group, the concentration of Glu in the C5aR-/- group was significantly higher than that in the WT group, and the C5a group was significantly lower than the C5a+C5aRA group. CONCLUSION: The deletion of the C5a receptor promotes NMDAR activity, which affects the toxic excitatory effect of NMDAR in NMO and regulates the neurotoxic effect of glutamic acid, thus participating in the pathogenesis of NMO.