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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Animal Models

Experimental allergic neuritis (EAN) has been considered as an animal model for human GBS. EAN is usually (but not always) a monophasic illness, which is induced by vaccination of rats, mice, rabbits, and guinea pigs with peripheral nerve homogenate or different myelin proteins such as P0, PMP 22, and P2 [34-37]. It presents with weakness and ataxia after a period of about 2 weeks after the vaccination. Perivascular T cell infiltration is noted 2-3 days before the onset of demyelination and paralysis [36, 37]. T cell infiltration results in activation of monocytes to tissue macrophages, which subsequently strip myelin and cause axonal injury by secreting cytokines such as tumor necrosis factor alpha. B cells also play a role in the pathogenesis of EAN, and autoantibodies against the myelin play a synergistic role in causing demyelination, after the blood-nerve barrier has become more permeable because of T cell activation and subsequent infiltration of macrophages [38]. Although the target antigen in EAN remains to be elusive, neurofascin 186 and gliomedin, which are involved in clustering of voltage-gated Na channels at the nodes of

Ranvier, have been suggested as potential antigenic targets [39, 40]. In the EAN model induced by vaccination with peripheral myelin in rat, antibodies to neurofas- cin and gliomedin cause dismantling of nodal organization and Na channel clusters, therefore leading to conduction block prior to onset of demyelination [39, 40].

B cell immunity, particularly autoantibodies to gangliosides, appears to have a primary role in the pathogenesis of GBS variants. Immunization of Japanese white rabbits with a bovine brain ganglioside mixture or isolated GM1 results in an AMAN phenotype: acute monophasic flaccid paralysis, seropositivity for anti-GM1 antibodies, axonal degeneration, IgG deposits at the nodes of Ranvier and lymphocytic infiltration in the periaxonal space, and lack of segmental demyelination [41, 42]. On the other hand, GQ1b and GD1a antibodies cause conduction block at the motor nerve terminals in a mouse model [25].

 
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