Establishment of a rat model for canine necrotizing meningoencephalitis (NME).
The pathogenesis of necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME) is still uncertain, although they are considered immune-mediated diseases. The purpose of the present study is to generate a rodent model(s) of these diseases. Rats were injected with rat cerebral or cerebellar homogenate. Rats injected with cerebral homogenate (Cbr) exhibited vacuolar or malacic changes mainly in the cerebral cortex. CD3-positive T cells and Iba-1-positive and CD163-negative microglia infiltrated and activated around the lesions. IgG deposited in the glial fibrillary acid protein (GFAP)-positive glia limitans from the early phase, and CD3-positive T cells attached to GFAP-positive astrocytes. Autoantibodies against GFAP were detected in the sera. These pathological features of Cbr rats were consistent with those of canine NME. In contrast, rats injected with cerebral homogenate (Cbe) exhibited demyelinating lesions with inflammatory reactions in the cerebellum, brainstem, and spinal cord. The presence of demyelination and autoantibodies against myelin proteins in Cbe rats was similar to murine experimental autoimmune encephalitis and differed from NME, NLE, and GME. All the present findings indicate that autoantibodies together with microglia and T cells may play a major role in the pathogenesis of idiopathic canine meningoencephalomyelitis.
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
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Park
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan auchidak@mail.ecc.u-tokyo.ac.jp.
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K
Uchida
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
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H
Nakayama
D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology*; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000276:immunology / Q000473:pathology*; D004285:Dogs; D007249:Inflammation / Q000662:veterinary; D008297:Male; D008590:Meningoencephalitis / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D009186:Myelin Sheath / Q000276:immunology; D009336:Necrosis / Q000662:veterinary; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies
animal model; autoantibody; dog; experimental autoimmune encephalitis (EAE); necrotizing meningoencephalitis (NME)