Graphene Oxide Nanosheets Hamper Glutamate Mediated Excitotoxicity and Protect Neuronal Survival In An In vitro Stroke Model

Abstract

AbstractSmall 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.