Cytokines in CNS Inflammation and Disease

Tansey, Malú G.; Wyss‐Coray, Tony

doi:10.1007/978-0-387-73894-9_5

Cited by 20 publications

(13 citation statements)

References 323 publications

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“…TNF-a has been demonstrated to play an important role in central nervous system neuroinflammation-mediated cell death in various neurodegenerative conditions. 37,38 In the present study, the cytokine was markedly increased in brain tissue after LPS administration. Here we demonstrate that citric acid treatment was associated with marked inhibitory effect on TNF-a production within brain tissue after LPS challenge.…”

Section: 26supporting

confidence: 54%

Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

Abdel-Salam

Youness²,

Mohammed³

et al. 2014

Journal of Medicinal Food

129

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Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 lg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-a) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-a, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

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Section: 26supporting

confidence: 54%

Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

Abdel-Salam

Youness²,

Mohammed³

et al. 2014

Journal of Medicinal Food

129

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“…In that sense, the environment created by the immune system will very likely affect α-syn levels. As noted in an earlier section, there are well-documented changes in cytokines in PD patients, both in the periphery and in the CNS (for an in-depth review see Tansey and Wyss-Coray, 2008). In parallel, it has been shown that the level of α-syn in human microglia is regulated by cytokine exposure (Bick et al, 2008).…”

Section: Role Of Microglia Activation In α-Syn-induced Degenerationmentioning

confidence: 89%

Neuroimmunological Processes in Parkinson's Disease and their Relation to α-Synuclein: Microglia as the Referee between Neuronal Processes and Peripheral Immunity

et al. 2013

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The role of neuroinflammation and the adaptive immune system in PD (Parkinson's disease) has been the subject of intense investigation in recent years, both in animal models of parkinsonism and in post-mortem PD brains. However, how these processes relate to and modulate α-syn (α-synuclein) pathology and microglia activation is still poorly understood. Specifically, how the peripheral immune system interacts, regulates and/or is induced by neuroinflammatory processes taking place during PD is still undetermined. We present herein a comprehensive review of the features and impact that neuroinflamation has on neurodegeneration in different animal models of nigral cell death, how this neuroinflammation relates to microglia activation and the way microglia respond to α-syn in vivo. We also discuss a possible role for the peripheral immune system in animal models of parkinsonism, how these findings relate to the state of microglia activation observed in these animal models and how these findings compare with what has been observed in humans with PD. Together, the available data points to the need for development of dual therapeutic strategies that modulate microglia activation to change not only the way microglia interact with the peripheral immune system, but also to modulate the manner in which microglia respond to encounters with α-syn. Lastly, we discuss the immune-modulatory strategies currently under investigation in animal models of parkinsonism and the degree to which one might expect their outcomes to translate faithfully to a clinical setting.

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“…Microglia, the myeloid-derived resident macrophages of the brain, play the primary role of immune surveillance and respond to environmental stress and immunological challenges (1, 2). Initial physical or pathogenic events in the CNS can trigger microglial expansion through recruitment of peripheral macrophages to the CNS, as a result of increased permeability of the BBB, differentiation from progenitor cells or proliferation of residual microglia (3).…”

Section: Introductionmentioning

confidence: 99%

Microglia Isolation from Adult Mouse Brain

Lee

Tansey

2013

Methods in Molecular Biology

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127

102

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Although microglia isolation from embryonic or postnatal mouse brain is possible using a number of different protocols, microglia isolation from adult brain is more challenging and often results in low yields. Here, we describe a protocol to isolate intact microglia from adult mouse brain for functional assays, immunocytochemistry and/or flow cytometry analysis. This protocol involves enzymatic dissociation in medium supplemented with dispase II, papain and DNase I followed by mechanical dissociation. Cell separation is achieved via percoll gradients of various densities. Microglia isolated using this protocol is suitable for flow cytometry analysis, RNA isolation for gene expression by real-time PCR or microarrays, and for functional assays including cytokine production, chemotaxis and phagocytosis.

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Cytokines in CNS Inflammation and Disease

Cited by 20 publications

References 323 publications

Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

Neuroimmunological Processes in Parkinson's Disease and their Relation to α-Synuclein: Microglia as the Referee between Neuronal Processes and Peripheral Immunity

Microglia Isolation from Adult Mouse Brain

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