Les cellules gliales

Boillée, Séverine; Lobsiger, Christian S.

doi:10.1051/medsci/2008242124

Cited by 5 publications

(6 citation statements)

References 21 publications

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“…Neuroinflammation is a prominent feature of murine ALS animal models [1], [5], [9], [10], [11], [12], [44]. Despite strong evidence for microglial activation and release of pro-inflammatory cytokines driving disease progression, anti-inflammatory strategies have been overall disappointing.…”

Section: Discussionmentioning

confidence: 99%

Influence of Methylene Blue on Microglia-Induced Inflammation and Motor Neuron Degeneration in the SOD1G93A Model for ALS

et al. 2012

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Mutations in SOD1 cause hereditary variants of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous, with toxicity deriving also from glia. In particular, microglia contribute to disease progression. Methylene blue (MB) inhibits the effect of nitric oxide, which mediates microglial responses to injury. In vivo 2P-LSM imaging was performed in ALS-linked transgenic SOD1G93A mice to investigate the effect of MB on microglia-mediated inflammation in the spinal cord. Local superfusion of the lateral spinal cord with MB inhibited the microglial reaction directed at a laser-induced axon transection in control and SOD1G93A mice. In vitro, MB at high concentrations inhibited cytokine and chemokine release from microglia of control and advanced clinical SOD1G93A mice. Systemic MB-treatment of SOD1G93A mice at early preclinical stages significantly delayed disease onset and motor dysfunction. However, an increase of MB dose had no additional effect on disease progression; this was unexpected in view of the local anti-inflammatory effects. Furthermore, in vivo imaging of systemically MB-treated mice also showed no alterations of microglia activity in response to local lesions. Thus although systemic MB treatment had no effect on microgliosis, instead, its use revealed an important influence on motor neuron survival as indicated by an increased number of lumbar anterior horn neurons present at the time of disease onset. Thus, potentially beneficial effects of locally applied MB on inflammatory events contributing to disease progression could not be reproduced in SOD1G93A mice via systemic administration, whereas systemic MB application delayed disease onset via neuroprotection.

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Section: Discussionmentioning

confidence: 99%

Influence of Methylene Blue on Microglia-Induced Inflammation and Motor Neuron Degeneration in the SOD1G93A Model for ALS

et al. 2012

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“…Microglia substantially contribute to motor neuron death and disease progression in mSOD1 mouse models for ALS [4], [5], [6], [11], [14], [15]. Our study using the SOD1 G93A -model provides substantial in vivo evidence that microglia-mediated inflammation in the CNS comprises two different phases with fluent transition: i) in preclinical stages, microglia is highly reactive as indicated by an enhanced injury-induced response including rapid soma migration and early phagocytic activity; ii) in clinical stages, activated ameboid microglia lose their target-directed response, but instead show spontaneous activity as a gain of function and a loss of its role as highly dynamic surveillants of the CNS [19].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, microglia and astrocytes substantially contribute to motor neuron death and disease progression [4], [5], [6], [11], [12], [13], [14], [15]. In the case of microglia, selective silencing of the mutant gene in the innate immune cells of the CNS and in macrophages in a SOD1-model has substantially slowed disease progression [4], [5].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS

et al. 2011

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Mutations in the enzyme superoxide dismutase-1 (SOD1) cause hereditary variants of the fatal motor neuronal disease Amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous: neurotoxicity is derived not only from mutant motor neurons but also from mutant neighbouring non-neuronal cells. In vivo imaging by two-photon laser-scanning microscopy was used to compare the role of microglia/macrophage-related neuroinflammation in the CNS and PNS using ALS-linked transgenic SOD1G93A mice. These mice contained labeled projection neurons and labeled microglia/macrophages. In the affected lateral spinal cord (in contrast to non-affected dorsal columns), different phases of microglia-mediated inflammation were observed: highly reactive microglial cells in preclinical stages (in 60-day-old mice the reaction to axonal transection was ∼180% of control) and morphologically transformed microglia that have lost their function of tissue surveillance and injury-directed response in clinical stages (reaction to axonal transection was lower than 50% of control). Furthermore, unlike CNS microglia, macrophages of the PNS lack any substantial morphological reaction while preclinical degeneration of peripheral motor axons and neuromuscular junctions was observed. We present in vivo evidence for a different inflammatory activity of microglia and macrophages: an aberrant neuroinflammatory response of microglia in the CNS and an apparently mainly neurodegenerative process in the PNS.

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“…The glutamate release blocker Riluzole is, at present, the only authorized treatment for ALS; however, Riluzole treatment extends life expectancy by only a few months ( 3 ). It has been demonstrated that treatment with Riluzole for 12 months reduces deterioration of muscular function by 33.4% and extends life expectancy by 2.77 months ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…At present, no treatments are able to prevent ALS progression. Riluzole is the only drug that is currently approved for the treatment of ALS and typically increases life expectancy by 3–6 months ( 3 – 7 ). Vitamin E is also often prescribed to patients with ALS due to its anti-oxidizing activity ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

GEMALS: A promising therapy for amyotrophic lateral sclerosis

Geffard¹,

Mangas²,

Bedat³

et al. 2018

Exp Ther Med

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that currently has no cure. At present, the only approved treatment for ALS is Riluzole, a glutamate release blocker that improves life expectancy by 3–6 months. ALS-Endotherapia (GEMALS) is a novel therapeutic approach to treat ALS and the aim of the present study was to investigate the potential beneficial effects of this novel treatment. A total of 31 patients with ALS were assessed in the current study. Deceleration of the disease was observed in 83.87% (P<0.0001) of patients and mean life expectancy was increased by 38 months. Motor functions, including breathing, walking, salivation, speech, swallowing and writing, were also improved in patients treated with GEMALS. The results of the present study demonstrate that long-term treatment with GEMALS has a curative effect in patients with ALS. Furthermore, the overall effectiveness of GEMALS was assessed using the ALS Assessment Questionnaire. The score improvement was 76.2 and 100% for men and women, respectively (P<0.0001), compared with the worldwide reference score. The present study provides a promising basis for the use of GEMALS as a therapeutic treatment for patients with ALS; however, these results must be confirmed in a double-blinded and randomized clinical trial.

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Les cellules gliales

Cited by 5 publications

References 21 publications

Influence of Methylene Blue on Microglia-Induced Inflammation and Motor Neuron Degeneration in the SOD1G93A Model for ALS

Influence of Methylene Blue on Microglia-Induced Inflammation and Motor Neuron Degeneration in the SOD1G93A Model for ALS

In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS

GEMALS: A promising therapy for amyotrophic lateral sclerosis

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