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Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocycline.

Zhang ZY, Zhang Z, Fauser U, Schluesener HJ - J. Cell. Mol. Med. (2008)

Bottom Line: Minocycline is known to have neuroprotective and anti-inflammatory effects.Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN.Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha in EAN sciatic nerves were greatly decreased by administration of minocycline as well.

View Article: PubMed Central - PubMed

Affiliation: Institute of Brain Research, University of Tuebingen, Germany.

ABSTRACT
Experimental autoimmune neuritis (EAN) is a widely used animal model of the human acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barré Syndrome. EAN is pathologically characterized by breakdown of the blood-nerve barrier, infiltration of reactive immune cells, local inflammation, demyelination in the peripheral nervous system and mechanical allodynia. Minocycline is known to have neuroprotective and anti-inflammatory effects. Furthermore, relieve of neuropathic pain following minocycline administration was observed in a variety of animal models. Here, we investigated the effects of minocycline on rat EAN. Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN. Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha in EAN sciatic nerves were greatly decreased by administration of minocycline as well. Furthermore, minocycline attenuated mechanical allodynia in EAN rats and greatly suppressed spinal microglial activation. All together, our data showed that minocycline could effectively suppress the peripheral and spinal inflammation (immune activation) to improve outcome in EAN rats, which suggests that minocycline may be considered as a potential candidate of pharmacological treatment for autoimmune-mediated neuropathies.

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Related in: MedlinePlus

Minocycline suppressed expression of interleukin (IL)-1β, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in sciatic nerves of EAN rats. Seventeen days after immunization, mRNA of sciatic nerves of both groups was isolated and relative expression levels analysed by RT-PCR. (A) Photos of gel electrophoresis with PCR products showed obviously reduced mRNA levels of IL-1(J, TNF-α and iNOS after treatment by minocycline. (B) Bar graph show semi-quantified results of imaging intensities relative to the housekeeping gene GAPDH. The unpaired t-test was performed to compare the differences (Graph Pad Prism 4.0 for windows). *P < 0.05 and **P < 0.01 compared to their respective control.
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fig05: Minocycline suppressed expression of interleukin (IL)-1β, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in sciatic nerves of EAN rats. Seventeen days after immunization, mRNA of sciatic nerves of both groups was isolated and relative expression levels analysed by RT-PCR. (A) Photos of gel electrophoresis with PCR products showed obviously reduced mRNA levels of IL-1(J, TNF-α and iNOS after treatment by minocycline. (B) Bar graph show semi-quantified results of imaging intensities relative to the housekeeping gene GAPDH. The unpaired t-test was performed to compare the differences (Graph Pad Prism 4.0 for windows). *P < 0.05 and **P < 0.01 compared to their respective control.

Mentions: iNOS and inflammatory cytokines IL-1β and TNF-α are up-regulated in EAN and known to play important roles in inflammatory progression of disease [19, 20]. Therefore, effects of minocycline on m-RNA levels of these mediators in EAN were investigated. Minocycline or PBS was given immediately following immunization until Day 17. As shown in Fig. 5, mRNA expressions of IL-1β, TNF-α and iNOS was significantly reduced by minocycline in sciatic nerves of EAN rats as compared to PBS controls.


Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocycline.

Zhang ZY, Zhang Z, Fauser U, Schluesener HJ - J. Cell. Mol. Med. (2008)

Minocycline suppressed expression of interleukin (IL)-1β, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in sciatic nerves of EAN rats. Seventeen days after immunization, mRNA of sciatic nerves of both groups was isolated and relative expression levels analysed by RT-PCR. (A) Photos of gel electrophoresis with PCR products showed obviously reduced mRNA levels of IL-1(J, TNF-α and iNOS after treatment by minocycline. (B) Bar graph show semi-quantified results of imaging intensities relative to the housekeeping gene GAPDH. The unpaired t-test was performed to compare the differences (Graph Pad Prism 4.0 for windows). *P < 0.05 and **P < 0.01 compared to their respective control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3823360&req=5

fig05: Minocycline suppressed expression of interleukin (IL)-1β, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in sciatic nerves of EAN rats. Seventeen days after immunization, mRNA of sciatic nerves of both groups was isolated and relative expression levels analysed by RT-PCR. (A) Photos of gel electrophoresis with PCR products showed obviously reduced mRNA levels of IL-1(J, TNF-α and iNOS after treatment by minocycline. (B) Bar graph show semi-quantified results of imaging intensities relative to the housekeeping gene GAPDH. The unpaired t-test was performed to compare the differences (Graph Pad Prism 4.0 for windows). *P < 0.05 and **P < 0.01 compared to their respective control.
Mentions: iNOS and inflammatory cytokines IL-1β and TNF-α are up-regulated in EAN and known to play important roles in inflammatory progression of disease [19, 20]. Therefore, effects of minocycline on m-RNA levels of these mediators in EAN were investigated. Minocycline or PBS was given immediately following immunization until Day 17. As shown in Fig. 5, mRNA expressions of IL-1β, TNF-α and iNOS was significantly reduced by minocycline in sciatic nerves of EAN rats as compared to PBS controls.

Bottom Line: Minocycline is known to have neuroprotective and anti-inflammatory effects.Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN.Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha in EAN sciatic nerves were greatly decreased by administration of minocycline as well.

View Article: PubMed Central - PubMed

Affiliation: Institute of Brain Research, University of Tuebingen, Germany.

ABSTRACT
Experimental autoimmune neuritis (EAN) is a widely used animal model of the human acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barré Syndrome. EAN is pathologically characterized by breakdown of the blood-nerve barrier, infiltration of reactive immune cells, local inflammation, demyelination in the peripheral nervous system and mechanical allodynia. Minocycline is known to have neuroprotective and anti-inflammatory effects. Furthermore, relieve of neuropathic pain following minocycline administration was observed in a variety of animal models. Here, we investigated the effects of minocycline on rat EAN. Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN. Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha in EAN sciatic nerves were greatly decreased by administration of minocycline as well. Furthermore, minocycline attenuated mechanical allodynia in EAN rats and greatly suppressed spinal microglial activation. All together, our data showed that minocycline could effectively suppress the peripheral and spinal inflammation (immune activation) to improve outcome in EAN rats, which suggests that minocycline may be considered as a potential candidate of pharmacological treatment for autoimmune-mediated neuropathies.

Show MeSH
Related in: MedlinePlus