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

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 car...

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Main Authors: Luise Schlotterose, François Cossais, Ralph Lucius, Kirsten Hattermann
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/4/2078
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author Luise Schlotterose
François Cossais
Ralph Lucius
Kirsten Hattermann
author_facet Luise Schlotterose
François Cossais
Ralph Lucius
Kirsten Hattermann
author_sort Luise Schlotterose
collection DOAJ
description 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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spelling doaj.art-26c05867cc8246e4b35065d854a4d3132024-02-23T15:19:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01254207810.3390/ijms25042078Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell ModelLuise Schlotterose0François Cossais1Ralph Lucius2Kirsten Hattermann3Institute of Anatomy, Kiel University, 24118 Kiel, GermanyInstitute of Anatomy, Kiel University, 24118 Kiel, GermanyInstitute of Anatomy, Kiel University, 24118 Kiel, GermanyInstitute of Anatomy, Kiel University, 24118 Kiel, GermanyBrain 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.https://www.mdpi.com/1422-0067/25/4/2078brain implantsforeign body reactionoxygen deprivationglucose deprivationreactive astrogliosisneuroinflammation
spellingShingle Luise Schlotterose
François Cossais
Ralph Lucius
Kirsten Hattermann
Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model
International Journal of Molecular Sciences
brain implants
foreign body reaction
oxygen deprivation
glucose deprivation
reactive astrogliosis
neuroinflammation
title Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model
title_full Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model
title_fullStr Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model
title_full_unstemmed Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model
title_short Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model
title_sort resveratrol alleviates the early challenges of implant based drug delivery in a human glial cell model
topic brain implants
foreign body reaction
oxygen deprivation
glucose deprivation
reactive astrogliosis
neuroinflammation
url https://www.mdpi.com/1422-0067/25/4/2078
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