Chemistry - A European Journal, 2023, e202301762

Graphene oxide nanosheets hamper glutamate mediated excitotoxicity and protect neuronal survival in an in vitro stroke model

Lorenza Tortella, Irene Santini, Neus Lozano, Kostas Kostarelos, Giada Cellot*, Laura Ballerini*

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. Here we exposed CNS cultures to oxygen-glucose deprivation (OGD) to mimic ischemic stroke in vitro, and we show that the delivery of small graphene oxide (s-GO) following OGD, during the endogenous build-up of secondary damage and excitotoxicity, improved neuronal survival. In a different paradigm, we reproduced excitotoxicity cell damage through exogenous glutamate application, and we observed that s-GO co-treatment protected neuronal integrity, potentially by directly downregulating the synaptic over-activation brought about by exogenous glutamate. In our proof-of-concept study, we suggest that s-GO may find novel applications in therapeutic developments for treating excitotoxicity-driven neural cell death.