To directly test our hypothesis that targeting CHI3L1 secreted from AQP4-IgG–induced astrocyte activation can alleviate demyelination lesions and motor dysfunction in NMO, we used a monoclonal anti-CHI3L1 neutralizing antibody that we previously demonstrated to block CHI3L1 actions in the brain (15). Here, AQP4 is linked to neuromyelitis optica.