Review of animal models of neuromyelitis optica

Jones, M. D.; Collongues, Nicolas; Seze, J. de; Kinoshita, Makoto; Nakatsuji, Yuji; Lévy, Michaël

doi:10.1016/j.msard.2012.06.003

Cited by 16 publications

(12 citation statements)

References 39 publications

(71 reference statements)

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“…The merits of the NMO model with MBP-EAE have already been reported [ 42 ]. Normal MBP-EAE takes a monophasic course without causing marked demyelination and axonal injury with full recovery.…”

Section: Discussionmentioning

confidence: 99%

“…Normal MBP-EAE takes a monophasic course without causing marked demyelination and axonal injury with full recovery. In addition, it is difficult to find infiltrations of neutrophil or eosinophils in Lewis rat EAE, induced by emulsion of guinea pig MBP and CFA without administrating pertussis toxin additionally [ 42 - 44 ]. In contrast, in the present model, the clinical severity and the lesion size of astrocytopathy is clearly dependent on the dose of the anti-AQP4 antibody and marked neutrophil infiltration and tissue vacuolation was only seen with high amounts of IgG (80 mg of hIgG NMO or 0.1–1 mg of E5415A).…”

Section: Discussionmentioning

confidence: 99%

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Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody

Kurosawa

Misu

Tokura

et al. 2015

acta neuropathol commun

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IntroductionNeuromyelitis optica (NMO), an autoimmune astrocytopathic disease associated with anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions preferentially involving the optic nerves and spinal cord. However, previous in-vivo experimental models injecting human anti-AQP4 antibodies only resulted in mild spinal cord lesions compared to NMO autopsied cases. Here, we investigated whether the formation of severe NMO-like lesions occurs in Lewis rats in the context of experimental autoimmune encephalomyelitis (EAE), intraperitoneally injecting incremental doses of purified human immunoglobulin-G from a NMO patient (hIgGNMO) or a high affinity anti-AQP4 monoclonal antibody (E5415A), recognizing extracellular domain of AQP4 made by baculovirus display method.ResultsNMO-like lesions were observed in the spinal cord, brainstem, and optic chiasm of EAE-rats with injection of pathogenic IgG (hIgGNMO and E5415A), but not in control EAE. Only in higher dose E5415A rats, there were acute and significantly severer clinical exacerbations (tetraparesis or moribund) compared with controls, within half day after the injection of pathogenic IgG. Loss of AQP4 was observed both in EAE rats receiving hIgGNMO and E5415A in a dose dependent manner, but the ratio of AQP4 loss in spinal sections became significantly larger in those receiving high dose E5415A up to about 50 % than those receiving low-dose E5415A or hIgGNMO less than 3 %. These lesions were also characterized by extensive loss of glial fibrillary acidic protein but relatively preserved myelin sheaths with perivascular deposition of IgG and C5b-9, which is compatible with post mortem NMO pathology. In high dose E5415A rats, massive neutrophil infiltration was observed especially at the lesion edge, and such lesions were highly vacuolated with partial demyelination and axonal damage. In contrast, such changes were absent in EAE rats receiving low-dose E5415A and hIgGNMO.ConclusionsIn the present study, we established a severe experimental NMO rat model with highly clinical exacerbation and extensive tissue destructive lesions typically observed in NMO patients, which has not adequately been realized in in-vivo rodent models. Our data suggest that the pathogenic antibodies could induce immune mediated astrocytopathy with mobilized neutrophils, resulted in early lesion expansion of NMO lesion with vacuolation and other tissue damages. (350/350)Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0259-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody

Kurosawa

Misu

Tokura

et al. 2015

acta neuropathol commun

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“…There is considerable interest in creating animal models of NMO for investigation of disease pathogenesis mechanisms and testing therapeutics [ 20 , 21 ]. The original animal models involved intraperitoneal injection of IgG purified from NMO patient serum in rats with pre-existing inflammation produced by sensitization to myelin oligodendrocyte protein (experimental autoimmune encephalomyelitis, EAE) [ 22 - 24 ] or by complete Freund’s adjuvant [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Neuromyelitis optica pathology in rats following intraperitoneal injection of NMO-IgG and intracerebral needle injury

Asavapanumas

Verkman

2014

acta neuropathol commun

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IntroductionAnimal models of neuromyelitis optica (NMO) are needed for drug testing and evaluation of NMO disease pathogenesis mechanisms.ResultsWe describe a novel passive-transfer model of NMO in which rats made seropositive for human anti-aquaporin-4 (AQP4) immunoglobulin G antibody (NMO-IgG) by intraperitoneal (IP) injections were subject to intracerebral needle injury. Following a single IP injection, NMO-IgG distributed rapidly to peripheral AQP4-expressing cells (kidney collecting duct, gastric glands, airways, skeletal muscle) and area postrema in brain, but not elsewhere in the central nervous system; however, no pathology was seen in brain, spinal cord, optic nerve or peripheral tissues. After testing various maneuvers to produce NMO-IgG-dependent pathology in brain, we found that transient puncture of brain parenchyma with a 28-gauge needle in NMO-IgG seropositive rats produced robust NMO pathology around the needle track, with loss of AQP4 and glial fibrillary acidic protein, granulocyte and macrophage infiltration, centrovascular deposition of activated complement, and blood–brain barrier disruption, with demyelination by 5 days. Pathology was not seen in rats receiving control (non-NMO) human IgG or in NMO-IgG-seropositive rats made complement-deficient by cobra venom factor. Interestingly, at 1 day a reversible, multifocal astrocytopathy was seen with loss of AQP4 and GFAP (but not myelin) in areas away from the needle track.ConclusionsNMO-IgG-seropositivity alone is not sufficient to cause NMO pathology in rats, but a single intracerebral needle insertion, without pre-existing inflammation or infusion of pro-inflammatory factors, was sufficient to produce robust NMO pathology in seropositive rats.

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“…Macrophages also participate in CDC and ADCC of NMO. So far, no single rodent model has proven to be a perfect representation of NMO in humans [ 123 ]. Commonly used experiments are obtained through passive transfer of NMO-IgG in certain contexts in rats or spinal cord cultures [ 124 ].…”

Section: Macrophages In Human Neuroimmune Diseases and Their Animamentioning

confidence: 99%

Double Roles of Macrophages in Human Neuroimmune Diseases and Their Animal Models

Fan

Zhang

Cheng

et al. 2016

Mediators of Inflammation

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Macrophages are important immune cells of the innate immune system that are involved in organ-specific homeostasis and contribute to both pathology and resolution of diseases including infections, cancer, obesity, atherosclerosis, and autoimmune disorders. Multiple lines of evidence point to macrophages as a remarkably heterogeneous cell type. Different phenotypes of macrophages exert either proinflammatory or anti-inflammatory roles depending on the cytokines and other mediators that they are exposed to in the local microenvironment. Proinflammatory macrophages secrete detrimental molecules to induce disease development, while anti-inflammatory macrophages produce beneficial mediators to promote disease recovery. The conversion of the phenotypes of macrophages can regulate the initiation, development, and recovery of autoimmune diseases. Human neuroimmune diseases majorly include multiple sclerosis (MS), neuromyelitis optica (NMO), myasthenia gravis (MG), and Guillain-Barré syndrome (GBS) and macrophages contribute to the pathogenesis of these neuroimmune diseases. In this review, we summarize the double roles of macrophage in neuroimmune diseases and their animal models to further explore the mechanisms of macrophages involved in the pathogenesis of these disorders, which may provide a potential therapeutic approach for these disorders in the future.

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Review of animal models of neuromyelitis optica

Cited by 16 publications

References 39 publications

Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody

Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody

Neuromyelitis optica pathology in rats following intraperitoneal injection of NMO-IgG and intracerebral needle injury

Double Roles of Macrophages in Human Neuroimmune Diseases and Their Animal Models

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