Astrocytes are the major glia cells in the central nervous system (CNS). Increasing evidence indicates that more than to be safe-guard and supporting cells for neurons, astrocytes play a broad spectrum of neuroprotective and pathological functions. Thus, they are compelling models to decipher mechanistic insights of glia cells to CNS insults and for the development of drugs. Edaravone is a free radical scavenger with the capacity to eliminate hydroxyl radicals and lipid peroxides. In this study, we examined the neuroprotective effects of edaravone in rat astrocytes challenged by hydrogen peroxide (H2O2) or bacterial lipopolysaccharides (LPS), respectively. We discovered that edaravone attenuated H2O2-induced oxidative stress by reactivating the Akt signaling axis and antagonistically restoring the expression of apoptosis associated regulators such as Bcl-2 and Caspase-3. Consistently, inhibition of Akt signaling by LY294002 attenuated the anti-oxidative activity of edaravone. In addition, edaravone mitigated LPS-induced morphological changes in astrocytes and alleviated the inflammatory activation and expression of TNF-α, IL-1β, IL-6 and NOS2. In summary, our data suggested that edavarone effectively protects astrocytes from oxidative stress or infectious insults, which may pave a new avenue for its application in preclinical research and human disease therapeutics.
Keywords: ALS, amyotrophic lateral sclerosis; C1q, complement component 1q; CNS, central nervous system; GFAP; GFAP, glial fibrillary acidic protein; H2O2, hydrogen peroxide; IL-1α, interleukin 1 alpha; IL-1β, interleukin 1beta; IL-6, interleukin 6; LPS, lipopolysaccharides; NOS2, nitric oxide synthase 2; TLRs, Toll-like receptors; TNF-α; TNF-α, tumor necrosis factor alpha; edaravone; free radical scavenger; oxidative stress; pro-inflammatory factors.
© 2020 The Author(s).