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Systemic Escherichia coli infection does not influence clinical symptoms and neurodegeneration in experimental autoimmune encephalomyelitis.

Kumar P, Friebe K, Schallhorn R, Moinfar Z, Nau R, Bähr M, Schütze S, Hein K - BMC Neurosci (2015)

Bottom Line: Analysis of the optic nerve and retinal ganglion cells revealed no significant changes in the extent of inflammatory infiltrates, demyelination and neurodegeneration after E. coli infection.We could not confirm the detrimental effect of lipopolysaccharide-induced systemic inflammation, a model frequently used to mimic the bacterial infection, previously observed in animal models of MS.Our results indicate that the effect of an acute E. coli infection on the course of MS is less pronounced than suspected and underline the need for adequate models to test the role of systemic infections in the pathogenesis of MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University Hospital, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany. singh_prats31@yahoo.co.in.

ABSTRACT

Background: Systemic infections can influence the course of multiple sclerosis (MS), especially by driving recurrent acute episodes. The question whether the infection enhances tissue damage is of great clinical importance and cannot easily be assessed in clinical trials. Here, we investigated the effects of a systemic infection with Escherichia coli, a Gram-negative bacterium frequently causing urinary tract infections, on the clinical course as well as on neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.

Methods: Rats were immunized with myelin oligodendrocyte glycoprotein (MOG1-125) and challenged intraperitoneally with live E. coli K1 in the preclinical or in the clinical phase of the disease. To ensure the survival of animals, antibiotic treatment with ceftriaxone was initiated 36 h after the infection and continued for 3 consecutive days.

Results: Systemic infection with E. coli did not influence the onset of clinical EAE symptoms or disease severity. Analysis of the optic nerve and retinal ganglion cells revealed no significant changes in the extent of inflammatory infiltrates, demyelination and neurodegeneration after E. coli infection.

Conclusions: We could not confirm the detrimental effect of lipopolysaccharide-induced systemic inflammation, a model frequently used to mimic the bacterial infection, previously observed in animal models of MS. Our results indicate that the effect of an acute E. coli infection on the course of MS is less pronounced than suspected and underline the need for adequate models to test the role of systemic infections in the pathogenesis of MS.

No MeSH data available.


Related in: MedlinePlus

Optical nerve (ON) histopathology for the early infection group. a, b Representative Luxol Fast Blue-stained cross sections of ONs of an animal infected with E. coli (a) and an animal from the respective control group (b). Representative examples for the number of infiltrated ED1 macrophages/activated microglia detected in the ON of an E. coli infected animal (c) and an animal from the non-infected control group (d). e, f Bielschowsky’s silver impregnation of an ON cross-section revealed no differences in axonal densities in a MOG immunized animal infected on day 7 post immunization (e) compared to a non-infected respective control animal (f). j Represents the quantitative data for numbers of surviving retinal ganglion cells (RGCs) of the animals infected with E. coli and of the animals without infection. g, h and i represent the quantitative data for demyelination, inflammatory infiltrates and for axonal counts in both the E. coli infected and control group (n = 15 infected; n = 13 control). Bar length for Luxol Fast Blue, ED1, 100 µm, and for Bielschowsky’s silver impregnation = 20 µm.
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Fig4: Optical nerve (ON) histopathology for the early infection group. a, b Representative Luxol Fast Blue-stained cross sections of ONs of an animal infected with E. coli (a) and an animal from the respective control group (b). Representative examples for the number of infiltrated ED1 macrophages/activated microglia detected in the ON of an E. coli infected animal (c) and an animal from the non-infected control group (d). e, f Bielschowsky’s silver impregnation of an ON cross-section revealed no differences in axonal densities in a MOG immunized animal infected on day 7 post immunization (e) compared to a non-infected respective control animal (f). j Represents the quantitative data for numbers of surviving retinal ganglion cells (RGCs) of the animals infected with E. coli and of the animals without infection. g, h and i represent the quantitative data for demyelination, inflammatory infiltrates and for axonal counts in both the E. coli infected and control group (n = 15 infected; n = 13 control). Bar length for Luxol Fast Blue, ED1, 100 µm, and for Bielschowsky’s silver impregnation = 20 µm.

Mentions: In optic nerves evaluated histopathologically at the end of the experiment, the extent of demyelination was similar in animals infected with E. coli on day 7 post immunization and the respective control animals [62.90 ± 9.43% (n = 15) vs. 79.18 ± 8.06% (n = 13); P = 0.20; Figure 4a, b, g]. Analysis of inflammatory infiltrates by ED1 staining also revealed no significant difference between the infection group and the control group in the “early infection” experiment [2.84 ± 0.39 (n = 15) vs. 3.45 ± 0.3 (n = 13) in the control group; P = 0.50; Figure 4c, d, h]. Bielschowsky silver impregnation was performed to assess the axonal density of the ON. The axonal loss in infected animals and control animals did not differ significantly [66 ± 7.64% (n = 15) vs. 82.19 ± 5.69% (n = 13); P = 0.10; Figure 4e, f, i].Figure 4


Systemic Escherichia coli infection does not influence clinical symptoms and neurodegeneration in experimental autoimmune encephalomyelitis.

Kumar P, Friebe K, Schallhorn R, Moinfar Z, Nau R, Bähr M, Schütze S, Hein K - BMC Neurosci (2015)

Optical nerve (ON) histopathology for the early infection group. a, b Representative Luxol Fast Blue-stained cross sections of ONs of an animal infected with E. coli (a) and an animal from the respective control group (b). Representative examples for the number of infiltrated ED1 macrophages/activated microglia detected in the ON of an E. coli infected animal (c) and an animal from the non-infected control group (d). e, f Bielschowsky’s silver impregnation of an ON cross-section revealed no differences in axonal densities in a MOG immunized animal infected on day 7 post immunization (e) compared to a non-infected respective control animal (f). j Represents the quantitative data for numbers of surviving retinal ganglion cells (RGCs) of the animals infected with E. coli and of the animals without infection. g, h and i represent the quantitative data for demyelination, inflammatory infiltrates and for axonal counts in both the E. coli infected and control group (n = 15 infected; n = 13 control). Bar length for Luxol Fast Blue, ED1, 100 µm, and for Bielschowsky’s silver impregnation = 20 µm.
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Related In: Results  -  Collection

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Fig4: Optical nerve (ON) histopathology for the early infection group. a, b Representative Luxol Fast Blue-stained cross sections of ONs of an animal infected with E. coli (a) and an animal from the respective control group (b). Representative examples for the number of infiltrated ED1 macrophages/activated microglia detected in the ON of an E. coli infected animal (c) and an animal from the non-infected control group (d). e, f Bielschowsky’s silver impregnation of an ON cross-section revealed no differences in axonal densities in a MOG immunized animal infected on day 7 post immunization (e) compared to a non-infected respective control animal (f). j Represents the quantitative data for numbers of surviving retinal ganglion cells (RGCs) of the animals infected with E. coli and of the animals without infection. g, h and i represent the quantitative data for demyelination, inflammatory infiltrates and for axonal counts in both the E. coli infected and control group (n = 15 infected; n = 13 control). Bar length for Luxol Fast Blue, ED1, 100 µm, and for Bielschowsky’s silver impregnation = 20 µm.
Mentions: In optic nerves evaluated histopathologically at the end of the experiment, the extent of demyelination was similar in animals infected with E. coli on day 7 post immunization and the respective control animals [62.90 ± 9.43% (n = 15) vs. 79.18 ± 8.06% (n = 13); P = 0.20; Figure 4a, b, g]. Analysis of inflammatory infiltrates by ED1 staining also revealed no significant difference between the infection group and the control group in the “early infection” experiment [2.84 ± 0.39 (n = 15) vs. 3.45 ± 0.3 (n = 13) in the control group; P = 0.50; Figure 4c, d, h]. Bielschowsky silver impregnation was performed to assess the axonal density of the ON. The axonal loss in infected animals and control animals did not differ significantly [66 ± 7.64% (n = 15) vs. 82.19 ± 5.69% (n = 13); P = 0.10; Figure 4e, f, i].Figure 4

Bottom Line: Analysis of the optic nerve and retinal ganglion cells revealed no significant changes in the extent of inflammatory infiltrates, demyelination and neurodegeneration after E. coli infection.We could not confirm the detrimental effect of lipopolysaccharide-induced systemic inflammation, a model frequently used to mimic the bacterial infection, previously observed in animal models of MS.Our results indicate that the effect of an acute E. coli infection on the course of MS is less pronounced than suspected and underline the need for adequate models to test the role of systemic infections in the pathogenesis of MS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University Hospital, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany. singh_prats31@yahoo.co.in.

ABSTRACT

Background: Systemic infections can influence the course of multiple sclerosis (MS), especially by driving recurrent acute episodes. The question whether the infection enhances tissue damage is of great clinical importance and cannot easily be assessed in clinical trials. Here, we investigated the effects of a systemic infection with Escherichia coli, a Gram-negative bacterium frequently causing urinary tract infections, on the clinical course as well as on neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.

Methods: Rats were immunized with myelin oligodendrocyte glycoprotein (MOG1-125) and challenged intraperitoneally with live E. coli K1 in the preclinical or in the clinical phase of the disease. To ensure the survival of animals, antibiotic treatment with ceftriaxone was initiated 36 h after the infection and continued for 3 consecutive days.

Results: Systemic infection with E. coli did not influence the onset of clinical EAE symptoms or disease severity. Analysis of the optic nerve and retinal ganglion cells revealed no significant changes in the extent of inflammatory infiltrates, demyelination and neurodegeneration after E. coli infection.

Conclusions: We could not confirm the detrimental effect of lipopolysaccharide-induced systemic inflammation, a model frequently used to mimic the bacterial infection, previously observed in animal models of MS. Our results indicate that the effect of an acute E. coli infection on the course of MS is less pronounced than suspected and underline the need for adequate models to test the role of systemic infections in the pathogenesis of MS.

No MeSH data available.


Related in: MedlinePlus