The central nervous system microenvironment imprints microglial inability to switch from pro- to anti-inflammatory phenotype

2014 ◽  
Vol 275 (1-2) ◽  
pp. 162
Author(s):  
Orit Matcovitch ◽  
Merav Cohen ◽  
Eyal David ◽  
Zohar Barnett-itzhaki ◽  
Hadas Keren-shaul ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Inflammatory Phenotype ◽  
The Central Nervous System ◽  
Anti Inflammatory

scholarly journals Inflammatory Cytokine Profile and Plasticity of Brain and Spinal Microglia in Response to ATP and Glutamate

2021 ◽  
Vol 15 ◽  
Author(s):  
Sam Joshva Baskar Jesudasan ◽  
Somnath J. Gupta ◽  
Matthew A. Churchward ◽  
Kathryn G. Todd ◽  
Ian R. Winship
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Interleukin 1 ◽  
Inflammatory Factors ◽  
Surrounding Environment ◽  
Glial Cultures ◽  
Inflammatory Phenotype ◽  
The Central Nervous System ◽  
Molecular Patterns

Microglia are the primary cells in the central nervous system that identify and respond to injury or damage. Such a perturbation in the nervous system induces the release of molecules including ATP and glutamate that act as damage-associated molecular patterns (DAMPs). DAMPs are detected by microglia, which then regulate the inflammatory response in a manner sensitive to their surrounding environment. The available data indicates that ATP and glutamate can induce the release of pro inflammatory factors TNF (tumor necrosis factor), IL-1β (interleukin 1 beta), and NO (nitric oxide) from microglia. However, non-physiological concentrations of ATP and glutamate were often used to derive these insights. Here, we have compared the response of spinal cord microglia (SM) relative to brain microglia (BM) using physiologically relevant concentrations of glutamate and ATP that mimic injured conditions in the central nervous system. The data show that ATP and glutamate are not significant modulators of the release of cytokines from either BM or SM. Consistent with previous studies, spinal microglia exhibited a general trend toward reduced release of inflammatory cytokines relative to brain-derived microglia. Moreover, we demonstrate that the responses of microglia to these DAMPs can be altered by modifying the biochemical milieu in their surrounding environment. Preconditioning brain derived microglia with media from spinal cord derived mixed glial cultures shifted their release of IL-1ß and IL-6 to a less inflammatory phenotype consistent with spinal microglia.

scholarly journals Inflammatory cytokine profile and plasticity of brain and spinal microglia in response to ATP and glutamate

2020 ◽  
Author(s):  
Sam Joshva Baskar Jesudasan ◽  
Somnath J Gupta ◽  
Matthew A Churchward ◽  
Kathryn Todd ◽  
Ian R Winship
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Interleukin 1 ◽  
Inflammatory Factors ◽  
Surrounding Environment ◽  
Glial Cultures ◽  
Inflammatory Phenotype ◽  
The Central Nervous System ◽  
Molecular Patterns

AbstractMicroglia are the primary cells in the central nervous system that identify and respond to injury or damage. Such a perturbation in the nervous system induces the release of molecules including ATP and glutamate that act as damage-associated molecular patterns (DAMPs). DAMPs are detected by microglia, which then regulate the inflammatory response in a manner sensitive to their surrounding environment. The available data indicates that ATP and glutamate can induce the release of pro inflammatory factors TNF (tumor necrosis factor), IL-1β (interleukin 1 beta) and NO (nitric oxide) from microglia. However, non-physiological concentrations of ATP and glutamate were often used to derive these insights. Here, we have compared the response of spinal cord microglia (SM) relative to brain microglia (BM) using physiologically relevant concentrations of glutamate and ATP that mimic injured conditions in the central nervous system. The data show that ATP and glutamate are not significant modulators of the release of cytokines from either BM or SM. Consistent with previous studies, spinal microglia exhibited a general trend towards reduced release of inflammatory cytokines relative to brain-derived microglia. Moreover, we demonstrate that the responses of microglia to these DAMPs can be altered by modifying the biochemical milieu in their surrounding environment. Preconditioning brain derived microglia with media from spinal cord derived mixed glial cultures shifted their release of IL-ß, IL-6 and IL-10 to a less inflammatory phenotype consistent with a spinal microglia.

Non-steroidal anti-inflammatory drugs and their effect on the nervous system: neurotoxicity, types, mechanism of occurrence

2021 ◽  
pp. 459-464
Author(s):  
Elmira Erfanovna Alimova ◽  
Elena Evgenievna Al-Rabadi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hearing Loss ◽  
Side Effects ◽  
World Health ◽  
The World ◽  
The Central Nervous System ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Health Organization

Currently, according to the World Health Organization, about 20% of the world's population takes non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are lipophilic substances that easily penetrate the blood-brain barrier and can cause side effects from the central nervous system. Neurotoxicity (headache, dizziness, insomnia, depression, depersonalization, psychosis, and tremor occur during the treatment with indomethacin; visual impairment, drowsiness - during the treatment with meloxicam; hearing loss - when taking salicylates) ranks second after gastrotoxicity. The article describes the mechanisms of neurotoxicity that occur when taking NSAIDs.

scholarly journals Central Nervous System Barriers Impact Distribution and Expression of iNOS and Arginase-1 in Infiltrating Macrophages During Neuroinflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniela C. Ivan ◽  
Sabrina Walthert ◽  
Giuseppe Locatelli
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Differential Distribution ◽  
General Ability ◽  
Border Regions ◽  
Arginase 1 ◽  
Tnf Α ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

In multiple sclerosis (MS) and other neuroinflammatory diseases, monocyte-derived cells (MoCs) traffic through distinct central nervous system (CNS) barriers and gain access to the organ parenchyma exerting detrimental or beneficial functions. How and where these MoCs acquire their different functional commitments during CNS invasion remains however unclear, thus hindering the design of MS treatments specifically blocking detrimental MoC actions. To clarify this issue, we investigated the distribution of iNOS+ pro-inflammatory and arginase-1+ anti-inflammatory MoCs at the distinct border regions of the CNS in a mouse model of MS. Interestingly, MoCs within perivascular parenchymal spaces displayed a predominant pro-inflammatory phenotype compared to MoCs accumulating at the leptomeninges and at the intraventricular choroid plexus (ChP). Furthermore, in an in vitro model, we could observe the general ability of functionally-polarized MoCs to migrate through the ChP epithelial barrier, together indicating the ChP as a potential CNS entry and polarization site for MoCs. Thus, pro- and anti-inflammatory MoCs differentially accumulate at distinct CNS barriers before reaching the parenchyma, but the mechanism for their phenotype acquisition remains undefined. Shedding light on this process, we observed that endothelial (BBB) and epithelial (ChP) CNS barrier cells can directly regulate transcription of Nos2 (coding for iNOS) and Arg1 (coding for arginase-1) in interacting MoCs. More specifically, while TNF-α+IFN-γ stimulated BBB cells induced Nos2 expression in MoCs, IL-1β driven activation of endothelial BBB cells led to a significant upregulation of Arg1 in MoCs. Supporting this latter finding, less pro-inflammatory MoCs could be found nearby IL1R1+ vessels in the mouse spinal cord upon neuroinflammation. Taken together, our data indicate differential distribution of pro- and anti-inflammatory MoCs at CNS borders and highlight how the interaction of MoCs with CNS barriers can significantly affect the functional activation of these CNS-invading MoCs during autoimmune inflammation.

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