The Pathogenesis of Canine Distemper Virus Induced Demyelination

Baumgärtner, Wolfgang; Alldinger, Susanne

doi:10.1007/0-387-25518-4_51

Cited by 13 publications

(17 citation statements)

References 85 publications

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“…In carnivores, it causes a systemic, often fatal disease, which is commonly associated with respiratory and/or gastrointestinal tract disorders and nervous system disturbances (7,8,19). Distemper leukoencephalitis (DL) with multifocal demyelination and different types of plaques is commonly found in distemper dogs (20,24,45,50,51,61), whereas gray matter lesions such as post-vaccinal encephalomyelitis, inclusion body polioencephalitis, and old dog encephalitis are rarely encountered (37).…”

Section: Introductionmentioning

confidence: 99%

“…Distemper leukoencephalitis (DL) with multifocal demyelination and different types of plaques is commonly found in distemper dogs (20,24,45,50,51,61), whereas gray matter lesions such as post-vaccinal encephalomyelitis, inclusion body polioencephalitis, and old dog encephalitis are rarely encountered (37). DL shares several neuropathologic similarities with multiple sclerosis (MS), and therefore represents a reliable animal model for human demyelinating diseases (7).…”

Section: Introductionmentioning

confidence: 99%

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Increase of Pro-Inflammatory Cytokine Expression in Non-Demyelinating Early Cerebral Lesions in Nervous Canine Distemper

et al. 2008

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Canine distemper virus (CDV) infection of the central nervous system results in lesions of the gray and white matter. While a biphasic disease process has been discussed for leukoencephalitis with a prominent loss of viral protein expression, polioencephalitis has been associated with virus persistence. Using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), expression of pro- and anti-inflammatory cytokines such as interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF)-alpha, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta were studied in the cerebra of distemper dogs with white matter lesions in the cerebellum. Additionally, cytokine values were correlated with the degree of CDV infection, major histocompatibility complex class II (MHC II) expression, and infiltration of CD4-, CD8-, and CD3epsilon-positive lymphocytes. Cerebral CDV infection was not associated with detectable light microscopic lesions or infiltration of B and T lymphocytes. However, an increasing number of CDV-antigen-positive cells was associated with an upregulation of MHC II antigen. RT-PCR results revealed a significant upregulation of IL-6, IL-8, IL-12, and TNF-alpha in the cerebra of distemper dogs, whereas IL-10 and TGF-beta showed no significant increase. Elevated cytokine values were directly related to the presence of CDV antigen and MHC II upregulation. However, succeeding increases of the latter did not result in an additional proportional elevation of cytokine expression values. In summary, the present study demonstrates the expression of pro-inflammatory cytokines by resident neural cells following CDV infection. Furthermore, the lack of light microscopic changes indicates that additional factors besides cytokines are necessary for the development of a distemper-characteristic neuropathology.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increase of Pro-Inflammatory Cytokine Expression in Non-Demyelinating Early Cerebral Lesions in Nervous Canine Distemper

et al. 2008

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“…Though both gray and white matter changes can be observed in distemper, demyelinating leukoencephalomyelitis (DL) represents the main sequel in dogs (5,42). Due to the morphological similarities between the neuropathological changes in DL and Multiple Sclerosis (MS), nervous distemper advanced to an important spontaneously occurring animal model of human demyelinating diseases (3,11,49). Due to the morphological similarities between the neuropathological changes in DL and Multiple Sclerosis (MS), nervous distemper advanced to an important spontaneously occurring animal model of human demyelinating diseases (3,11,49).…”

Section: Introductionmentioning

confidence: 99%

“…Types of plaques in canine distemper are distinguished according to their morphological appearance and are presumed to be related to the age of the lesion (5,18,41,51). In contrast, plaque progression seems to be an immunopathologic process associated with a decrease or an elimination of virus antigen within lesions, strong upregulation of major histocompatibility complex (MHC) class II and an infiltration of CD4-and CD8-positive lymphocytes, plasma cells and macrophages (3,42). Initiation of demyelination has been ascribed to a direct action of the virus, infiltrating CD8-positive cytotoxic T cells and an upregulation of proinflammatory cytokines (4,17,20).…”

Section: Introductionmentioning

confidence: 99%

Axonal Pathology and Loss Precede Demyelination and Accompany Chronic Lesions in a Spontaneously Occurring Animal Model of Multiple Sclerosis

Seehusen

Baumgärtner

2010

Brain Pathology

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Axonal damage has been highlighted recently as a cause of neurological disability in various demyelinating diseases, including multiple sclerosis, either as a primary pathological change or secondary due to myelin loss. To characterize and quantify axonal damage and loss in canine distemper demyelinating leukoencephalomyelitis (DL), formalin-fixed paraffin-embedded cerebella were investigated histochemically and immunohistochemically using the modified Bielschowsky's silver stain as well as antibodies against nonphosphorylated (n-NF), phosphorylated neurofilament (p-NF) and beta-amyloid precursor protein (beta-APP). Injured axons characterized by immunoreactivity against n-NF and beta-APP were detected in early distemper lesions without demyelination. In subacute and chronic demyelinating lesions the number of injured axons increased. Moreover, a significant decrease in axonal density was observed within lesions and in the normal appearing white matter in DL as determined by morphometric analyses using Bielschowsky's silver stain and p-NF immunohistochemistry. Summarized, the observed findings indicate that axonal damage (i) occurs early in DL; (ii) can be detected before myelin loss; and (iii) represents a pivotal feature in advanced lesions. It must be postulated that axonal damage plays an important role in the initial phase as a primary event and during progression of nervous distemper as a result of demyelination.

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“…Despite the fact that infection of dogs may result in an array of clinical forms, immunosuppression and demyelinating leukoencephalitis characterize the main outcome in this species (Krakowka et al, 1985;Appel, 1987). Dogs naturally infected with CDV may also serve as alternative animal models to study the pathogenesis of demyelinisation in various diseases, including multiple sclerosis (Baumgärtner and Alldinger, 2005;Vandevelde and Zurbriggen, 2005;Beineke et al, 2009). Canine 4 parainfluenza virus-2 (CPIV-2) is another pathogen that affects dogs.…”

Section: Introductionmentioning

confidence: 99%

The antiviral activity of six South African plants traditionally used against infections in ethnoveterinary medicine

Bagla

McGaw

Eloff

2012

Veterinary Microbiology

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Viral infections remain a major threat to humans and animals and there is a crucial need for new antiviral agents especially with the development of resistant viruses. The hexane, dichloromethane, acetone and methanol extracts of six plant species selected for their traditional use against infections were tested for in vitro antiviral activity against canine distemper virus (CDV), canine Parainfluenza virus-2 (CPIV-2), feline herpesvirus-1 (FHV-1) and lumpy skin disease virus (LSDV). All extracts were tested for their cytotoxicity using a colorimetric tetrazolium-based (MTT) assay and were tested for antiviral efficacy at concentrations below CC50 values on the various cell types used in the study. The antiviral activity of extracts was tested using virucidal and attachment assays. In the virucidal assay, extracts were incubated with virus prior to infection. The most potent inhibition was observed with the acetone and methanol extracts of Podocarpus henkelii against CDV and LSDV, which inhibited replication of the viruses by >75% at 3 ug/ml with selectivity index (SI) values ranging between 12 and 45. Excellent activity was also found with the hexane extracts of Plumbago zeylanica and Carissa edulis against CDV, with the extracts reducing viral-induced CPE by 50% and 75% respectively. The 2 hexane extract of Carissa edulis had moderate activity against FHV-1 with EC50 <70 ug/ml and SI value <2. Only the acetone extract of Podocarpus henkelii moderately inhibited replication of LSD virus in the attachment assay, with low activity in other extracts. Of the four extracts with significant antiviral activity, two were prepared from Podocarpus henkelii. Therefore, future work will focus on isolating and characterizing the substance(s) responsible for bioactivity in extracts of this species.

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The Pathogenesis of Canine Distemper Virus Induced Demyelination

Cited by 13 publications

References 85 publications

Increase of Pro-Inflammatory Cytokine Expression in Non-Demyelinating Early Cerebral Lesions in Nervous Canine Distemper

Increase of Pro-Inflammatory Cytokine Expression in Non-Demyelinating Early Cerebral Lesions in Nervous Canine Distemper

Axonal Pathology and Loss Precede Demyelination and Accompany Chronic Lesions in a Spontaneously Occurring Animal Model of Multiple Sclerosis

The antiviral activity of six South African plants traditionally used against infections in ethnoveterinary medicine

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