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

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. Here we exposed CNS cultures to oxygen‐glucose deprivation (OGD) to mimic ischemic stroke in vitro, and we 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, 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.

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective

“…Glutamate-mediated excitotoxicity is affiliated with the pathogenesis of various brain maladies, ranging from ischemic stroke or brain injury to Parkinson's and Alzheimer's disease. 373 The same GO was reported to downregulate presynaptic glutamate release in rats, highlightingu possible uses with regards to stress-related neurological diseases. 374 Nonmammalian models have also proved themselves as valuable alternatives in evaluating neurological toxicity.…”

“…Small GO (<500 nm) has also been used in proof-of-concept studies in applied neurology, showing benefit in limiting excitotoxicity in an in vitro Wistar rat model of ischemic stroke featuring oxygen-glucose deprivation. Glutamate-mediated excitotoxicity is affiliated with the pathogenesis of various brain maladies, ranging from ischemic stroke or brain injury to Parkinson’s and Alzheimer’s disease . The same GO was reported to downregulate presynaptic glutamate release in rats, highlightingu possible uses with regards to stress-related neurological diseases …”