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

Abstract

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.

Keywords: Astrocytes; ECM proteins; Microglia; Neurodegenerative diseases; Neuroinflammation; TNFα.