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 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

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

Neuroinflammation is both cause and effect of many neurodegenerative disorders. Activation of astrocytes and microglia leads to the release of cytokines and reactive oxygen species followed by blood-brain barrier leakage and neurotoxicity. Transient neuroinflammation is considered to be largely protective, however, chronic neuroinflammation contributes to the pathology of Alzheimer’s disease, multiple sclerosis, traumatic brain injury, and many more. In this study, we focus on the aspect of cytokine-induced neuroinflammation in human microglia and astrocytes. Here we show by mRNA and protein analysis that cytokines, released not only by microglia but also by astrocytes, lead to a circuit of proinflammatory activation. Moreover, we present how the natural compound resveratrol can stop the circuit of proinflammatory activation and facilitate return to resting conditions. These results will contribute to distinguishing between the causes and the effects of neuroinflammation, a better understanding of underlying mechanisms, and potential treatment options

Resveratrol Mitigates Metabolism in Human Microglia Cells

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