Chronic Experimental Allergic Neuritis in Lewis Rats

Abstract

An experimental chronic relapsing demyelinating neuropathy was produced by immunizing adult Lewis rats with bovine myelin in low (2.5 mg) and high (5 mg) doses, with and without Mycobacterium tuberculosis in the adjuvant. Each regime produced a similar disease course: acute severe hind limb weakness was followed by apparent recovery and then reappearance of mild neurological deficit with occasional spontaneous exacerbations. The partially recovered animals were relatively resistant to reimmunization with myelin. Immunization of four-week-old rats with myelin in complete adjuvant produced disease with a similar course. Subsequent immunization of these juvenile rats with adjuvant alone precipitated exacerbations. In the late stages, the prominent changes in peripheral nerves and nerve roots were axon loss, axonal regeneration and remyelination while inflammatory cell infiltration was confined to occasional foci. Onion bulb formation was extremely common in the dorsal root ganglia and affected in particular the nerve fibres close to the dorsal root ganglion cells. The cells forming the onion bulbs resembled the satellite cells surrounding the axon hillocks. Onion bulb formation also occurred in the portion of the ventral roots adjacent to the dorsal root ganglion but was rare elsewhere. Immunocytochemistry revealed only occasional lymphocyte infiltration but there was increased Class I and Class II MHC antigen expression throughout the peripheral nervous system. The results are relevant to the interpretation of biopsies from patients with chronic demyelinating neuropathy of possible inflammatory or autoimmune origin.

The effects of prophylactic cyclosporin A on experimental allergic neuritis (EAN) in the Lewis rat. Induction of relapsing EAN using low dose cyclosporin A

“…Brosnan et al (1984) found that 30% of male Lewis rats developed chronic disease after BIR myelin-induced EAN. Adam et al (1989) found that one of nine Lewis rats inoculated with 2.5 mg and eight of nine rats inoculated with 5.0 mg myelin developed an early relapse of EAN. In-creased incidence of relapses with higher doses of inoculum has also been shown by Harvey et al (1987) in EAN in rabbits.…”

Selective Vulnerability of Peripheral Nerves in Avian Riboflavin Deficiency Demyelinating Polyneuropathy

“…Demyelinative changes in both peripheral nerves and spinal nerve roots have also been reported in hypertrophic hereditary motor and sensory neuropathy, 4 protein zero-deficient mice, 9,26 peripheral myelin protein-22 deficient mice, 40 Trembler mice, 2 and Trembler-J mice 13 and in animal models of inflammatory demyelinating neuropathy. 1,14,17,24,38,39 In 2 mice with POEMS, which is a monoclonal plasma cell disorder characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal gammopathy (M), and skin changes (S), spinal nerve roots and sural nerves showed the same pathologic changes of demyelination, remyelination, and inflammatory cell infiltration, 42,47 and in 3 cases of diabetic neuropathy, there was severe loss of both large and small MF in sural nerves while segmental demyelination and remyelination was the main finding in both dorsal and ventral spinal roots. 32 Distal intramuscular and subcutaneous MF have rarely been examined in demyelinating peripheral neuropathies, although skin biopsy has been used in the diagnosis of disorders involving unmyelinated 21 and myelinated 11,23,25 fiber disorders.…”

Chronic inflammatory demyelinating polyneuropathy

“…Hinweise kommen auch vom Tiermodell, der experimentellen autoimmunen Neuritis (EAN), einem akut monophasisch verlaufenden Modell des Guillain-Barré-Syndroms,das manchmal bei Ratten und insbesondere auch bei Kaninchen einen chronisch schubförmigen Verlauf nehmen kann [32,2]. In diesem Tiermodell lassen sich auf morphologischer Ebene deutliche Ähnlichkeiten zur humanen Form der CIDP finden: Zeichen chronischer Entzündung mit zellulären Infiltraten,Ödem und Schwann-Zell-Proliferation mit Zwiebelschalenbildung.…”

“…Das gute Ansprechen betroffener Patienten auf eine Plasmaseparation deutet auf eine Beteiligung des humoralen Immunsystems hin [2,98]. Unlängst konnte durch den Transfer von Serum betroffener Patienten gezeigt werden, dass sich die elektrophysiologischen und pathologischen Charakteristika der Erkrankung auf Tiere übertragen lassen [111].…”