Breaking the circulus vitiosus of neuroinflammation: Resveratrol attenuates the human glial cell response to cytokines

Schlotterose, Luise; Cossais, François; Lucius, Ralph; Hattermann, Kirsten

doi:10.1016/j.biopha.2023.114814

Cited by 10 publications

(7 citation statements)

References 35 publications

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“…Astrocyte reactivity also contributes to the proinflammatory milieu [5] and is linked to reactive astrogliosis, causing specific functional and structural changes in the brain tissue. The lectin galectin-3 was used in this study as a marker for reactive astrocytes because of its modulating role in the Notch1 signaling pathway, which has a significant impact on astrocyte reactivity [34].…”

Section: Discussionmentioning

confidence: 99%

“…To date, there are only a few examples of U.S. Food and Drug Administration (FDA)-approved brain implants for local drug delivery [4], as the implantation of foreign bodies into the brain tissue itself causes damage. The surgical procedure leads to bleeding and non-residual immune cell invasion and results in an inflammatory reaction [5]. Furthermore, the loss of perfusion leads to hypoxia and an impeded nutrient supply in the surrounding tissue.…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model

Schlotterose,

Cossais,

Lucius

et al. 2024

IJMS

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Brain diseases are oftentimes life-threatening and difficult to treat. The local administration of drug substances using brain implants can increase on-site concentrations and decrease systemic side effects. However, the biocompatibility of potential brain implant materials needs to be evaluated carefully as implants can trigger foreign body reactions, particularly by increasing the microglia and astrocyte reactivity. To date, these tests have been frequently conducted in very simple in vitro models, in particular not respecting the key players in glial cell reactions and the challenges of surgical implantation characterized by the disruption of oxygen and nutrient supply. Thus, we established an in vitro model in which we treated human glial cell lines with reduced oxygen and glucose levels. The model displayed cytokine and reactive oxygen species release from reactive microglia and an increase in a marker of reactive astrocytes, galectin-3. Moreover, the treatment caused changes in the cell survival and triggered the production of hypoxia-inducible factor 1α. In this comprehensive platform, we demonstrated the protective effect of the natural polyphenol resveratrol as a model substance, which might be included in brain implants to ease the undesired glial cell response. Overall, a glial-cell-based in vitro model of the initial challenges of local brain disease treatment may prove useful for investigating new therapy options.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model

Schlotterose,

Cossais,

Lucius

et al. 2024

IJMS

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“…Resveratrol is a polyphenol and phytoalexin derived from the skin of grapes, red wine, Japanese knotweeds, and peanuts. It has been shown that resveratrol has extensive properties including antioxidant, improving microglial-mediated inflammatory factor, and neuroprotective properties ( 244 – 246 ). Resveratrol showed excellent anti-depressive activity with an obvious improvement in depressive-like behavior tests.…”

Section: Drugs Targeting Microglia To Alter Neurogenesis For Treating...mentioning

confidence: 99%

Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics

Fang,

Wu,

Guo

et al. 2023

Front. Immunol.

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Adult hippocampal neurogenesis generates functional neurons from neural progenitor cells in the hippocampal dentate gyrus (DG) to complement and repair neurons and neural circuits, thus benefiting the treatment of depression. Increasing evidence has shown that aberrant microglial activity can disrupt the appropriate formation and development of functional properties of neurogenesis, which will play a crucial role in the occurrence and development of depression. However, the mechanisms of the crosstalk between microglia and adult hippocampal neurogenesis in depression are not yet fully understood. Therefore, in this review, we first introduce recent discoveries regarding the roles of microglia and adult hippocampal neurogenesis in the etiology of depression. Then, we systematically discuss the possible mechanisms of how microglia regulate adult hippocampal neurogenesis in depression according to recent studies, which involve toll-like receptors, microglial polarization, fractalkine-C-X3-C motif chemokine receptor 1, hypothalamic-pituitary-adrenal axis, cytokines, brain-derived neurotrophic factor, and the microbiota-gut-brain axis, etc. In addition, we summarize the promising drugs that could improve the adult hippocampal neurogenesis by regulating the microglia. These findings will help us understand the complicated pathological mechanisms of depression and shed light on the development of new treatment strategies for this disease.

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“…The antioxidant resveratrol (3, 4′, 5 trihydroxystilbene) is known to support the microglia M2 phenotype and inhibit neuroinflammation [ 11 , 12 ]. Resveratrol is a polyphenol found in different plants, produced as a reaction to injury or as protection against fungi.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Mitigates Metabolism in Human Microglia Cells

et al. 2023

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The recognition of the role of microglia cells in neurodegenerative diseases has steadily increased over the past few years. There is growing evidence that the uncontrolled and persisting activation of microglial cells is involved in the progression of diseases such as Alzheimer’s or Parkinson’s disease. The inflammatory activation of microglia cells is often accompanied by a switch in metabolism to higher glucose consumption and aerobic glycolysis. In this study, we investigate the changes induced by the natural antioxidant resveratrol in a human microglia cell line. Resveratrol is renowned for its neuroprotective properties, but little is known about its direct effect on human microglia cells. By analyzing a variety of inflammatory, neuroprotective, and metabolic aspects, resveratrol was observed to reduce inflammasome activity, increase the release of insulin-like growth factor 1, decrease glucose uptake, lower mitochondrial activity, and attenuate cellular metabolism in a 1H NMR-based analysis of whole-cell extracts. To this end, studies were mainly performed by analyzing the effect of exogenous stressors such as lipopolysaccharide or interferon gamma on the metabolic profile of microglial cells. Therefore, this study focuses on changes in metabolism without any exogenous stressors, demonstrating how resveratrol might provide protection from persisting neuroinflammation.

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Breaking the circulus vitiosus of neuroinflammation: Resveratrol attenuates the human glial cell response to cytokines

Cited by 10 publications

References 35 publications

Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model

Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model

Roles of microglia in adult hippocampal neurogenesis in depression and their therapeutics

Resveratrol Mitigates Metabolism in Human Microglia Cells

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