Graphene Oxide Nanosheets Reduce Astrocyte Reactivity to Inflammation and Ameliorate Experimental Autoimmune Encephalomyelitis

氧化石墨烯纳米片降低星形胶质细胞对炎症的反应性并改善实验性自身免疫性脑脊髓炎

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作者:Giuseppe Di Mauro, Roberta Amoriello, Neus Lozano, Alberto Carnasciali, Daniele Guasti, Maurizio Becucci, Giada Cellot, Kostas Kostarelos, Clara Ballerini, Laura Ballerini

Abstract

In neuroinflammation, astrocytes play multifaceted roles that regulate the neuronal environment. Astrocytes sense and respond to pro-inflammatory cytokines (CKs) and, by a repertoire of intracellular Ca2+ signaling, contribute to disease progression. Therapeutic approaches wish to reduce the overactivation in Ca2+ signaling in inflammatory-reactive astrocytes to restore dysregulated cellular changes. Cell-targeting therapeutics might take advantage by the use of nanomaterial-multifunctional platforms such as graphene oxide (GO). GO biomedical applications in the nervous system involve therapeutic delivery and sensing, and GO flakes were shown to enable interfacing of neuronal and glial membrane dynamics. We exploit organotypic spinal cord cultures and optical imaging to explore Ca2+ changes in astrocytes, and we report, when spinal tissue is exposed to CKs, neuroinflammatory-associated modulation of resident glia. We show the efficacy of GO to revert these dynamic changes in astrocytic reactivity to CKs, and we translate this potential in an animal model of immune-mediated neuroinflammatory disease.

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