Low Frequency Ultrasound With Injection of NMO-IgG and Complement Produces Lesions Different From Experimental Autoimmune Encephalomyelitis Mice

Abstract

Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune disease of the central nervous system, mainly targets the optic nerve and spinal cord. To date, all attempts at the establishment of NMOSD animal models have been based on neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and mimic the disease in part. To solve this problem, we developed a rodent model by opening the blood-brain barrier (BBB) with low frequency ultrasound, followed by injection of NMO-IgG from NMOSD patients and complement to mice suffering pre-existing neuroinflammation produced by experimental autoimmune encephalomyelitis (EAE). In this study, we showed that ultrasound with NMO-IgG and complement caused marked inflammation and demyelination of both spinal cords and optic nerves compared to blank control group, as well as glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) loss of spinal cords and optic nerves compared to EAE mice and EAE mice with only BBB opening. In addition, magnetic resonance imaging (MRI) revealed optic neuritis with spinal cord lesions. We further demonstrated eye segregation defects in the dorsal lateral geniculate nucleus (dLGN) of these NMOSD mice.

GV‐971 attenuates the progression of neuromyelitis optica in murine models and reverses alterations in gut microbiota and associated peripheral abnormalities

“…Building on the above work, we evaluated the therapeutic potential of GV‐971 in a reported NMOSD mouse model. 43 In this NMOSD model, we utilized young mice that were 7 weeks old. We employed low‐frequency focused ultrasound combined with the microbubble technique (MELFUS) and complement injection in addition to the administration of NMO‐IgG (Figure 2A ).…”

“…Building on the above work, we evaluated the therapeutic potential of GV‐971 in a reported NMOSD mouse model 43 . In this NMOSD model, we utilized young mice that were 7 weeks old.…”

“…To establish the EAE model in young mice, we followed a published protocol. 43 Briefly, on day 0, the mice were randomly assigned to different groups ( n = 5). After anesthetizing the mice with isoflurane, we subcutaneously injected an emulsion containing 2 mg/mL MOG 35‐55 and 4 mg/mL complete Freund's adjuvant (CFA) in equal volumes (10 μL each), which had been homogenized for 1 h in a 40 mL brown glass vial.…”

“…To establish the EAE model in young mice, we followed a published protocol 43 . Briefly, on day 0, the mice were randomly assigned to different groups ( n = 5).…”