Table 3.

Comparison of NMO human pathology to current experimental animal models

Model (ref)	Human NMO 58, 86	IL‐1 beta/NMO‐IgG model 40	NMO‐IgG/human complement injection model 89, 90, 91	EAE/NMO‐IgG model 8	EAE/recombinant human AQP4 Ab model 6	AQP4‐specific T cell/NMO‐IgG 77	EAE/NMO‐IgG model 37	NMO‐IgG/CFA pretreated models 38
Species	Human	Lewis rat	CD1 mice, AQP4 KO mice, nude mice	Lewis rat	Lewis rat	Lewis rat	Lewis rat	Lewis rat
Method	Human disease	Intracerebral injection of cytokine and NMO‐IgG	Repeated intracerebral injection of NMO‐IgG and human complement into brain parenchyma and ventricles	Passive transfer of MBP T cell line (passive EAE) + NMO‐IgG	Recombinant human AQP4 Ab into the retrobulbar venous plexus of MBP EAE	Intraperitoneal injecting AQP4‐specific T cells/intraperitoneal NMO‐IgG	Immunization with MBP inducing EAE/intraperitoneal NMO‐IgG	CFA treatment; intraperitoneal injection of NMO‐IgG
CNS trauma	No	Yes	Yes	No	No	No	No	No
Demyelination	Yes	No	Yes	No	No (only perivascular myelin vacuolization)	No	Unknown	Unknown
T lymphocyte inflammation	Yes	Yes	Yes/(No in nude mice)	Yes	Yes	Yes	Yes	Limited
Macrophage/microglial reaction	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Granulocyte infiltration	Neutrophil and eosinophil	Neutrophil	Neutrophil	Neutrophil	Unknown	Neutrophil	Neutrophil and eosinophil	Granulocytes
AQP4 loss	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
GFAP loss	Yes (variable)	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Other astrocyte pathology	Both astrocytic lytic and sublytic changes	Loss of astrocytes	Loss of astrocytes	Swollen astrocyte, astrocytic destruction	Loss of astrocytic bodies and processes	Unknown	Balloon‐like dying astrocyte	Swelling of astrocytes
Immune complex deposition	Perivascular complement and IgG deposition	Perivascular and astrocytic complement deposition	Vasculocentric complement deposition	Perivascular IgG and complement deposition	Perivascular IgG and complement deposition	Perivascular IgG and complement deposition	Perivascular deposition of Ig and complement	Perivascular deposition of Ig and complement
Axonal pathology	Yes (severe)	Unknown	Yes	No	Unknown	Unknown	Unknown	Unknown