Small graphene oxide (s-GO) nanosheets reversibly downregulate central nervous system (CNS) excitatory synapses, with potential developments as future therapeutic tools to treat neuro-disorders characterized by altered glutamatergic transmission. Excitotoxicity, namely cell death triggered by exceeding ambient glutamate fueling over-activation of excitatory synapses, is a pathogenic mechanism shared by several neural diseases, from ischemic stroke to neurodegenerative disorders. In this work, CNS cultures were exposed to oxygen-glucose deprivation (OGD) to mimic ischemic stroke in vitro, and it is show that the delivery of s-GO following OGD, during the endogenous build-up of secondary damage and excitotoxicity, improved neuronal survival. In a different paradigm, excitotoxicity cell damage was reproduced through exogenous glutamate application, and s-GO co-treatment protected neuronal integrity, potentially by directly downregulating the synaptic over-activation brought about by exogenous glutamate. This proof-of-concept study suggests that s-GO may find novel applications in therapeutic developments for treating excitotoxicity-driven neural cell death.
Graphene Oxide Nanosheets Hamper Glutamate Mediated Excitotoxicity and Protect Neuronal Survival In An In vitro Stroke Model / Tortella, Lorenza; Santini, Irene; Lozano, Neus; Kostarelos, Kostas; Cellot, Giada; Ballerini, Laura. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 29:67(2023), pp. 1-10. [10.1002/chem.202301762]
Graphene Oxide Nanosheets Hamper Glutamate Mediated Excitotoxicity and Protect Neuronal Survival In An In vitro Stroke Model
Tortella, Lorenza;Santini, Irene;Cellot, Giada;Ballerini, Laura
2023-01-01
Abstract
Small graphene oxide (s-GO) nanosheets reversibly downregulate central nervous system (CNS) excitatory synapses, with potential developments as future therapeutic tools to treat neuro-disorders characterized by altered glutamatergic transmission. Excitotoxicity, namely cell death triggered by exceeding ambient glutamate fueling over-activation of excitatory synapses, is a pathogenic mechanism shared by several neural diseases, from ischemic stroke to neurodegenerative disorders. In this work, CNS cultures were exposed to oxygen-glucose deprivation (OGD) to mimic ischemic stroke in vitro, and it is show that the delivery of s-GO following OGD, during the endogenous build-up of secondary damage and excitotoxicity, improved neuronal survival. In a different paradigm, excitotoxicity cell damage was reproduced through exogenous glutamate application, and s-GO co-treatment protected neuronal integrity, potentially by directly downregulating the synaptic over-activation brought about by exogenous glutamate. This proof-of-concept study suggests that s-GO may find novel applications in therapeutic developments for treating excitotoxicity-driven neural cell death.File | Dimensione | Formato | |
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