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

In vitro models of ischemic stroke based on the cell damage of dissociated central nervous system cultures due to glucose and oxygen deprivation (OGD) or to the exposure to a high concentration of glutamate (Glut) were used to establish that s-GO, applied during the glutamate mediated excitotoxic cascade, by modulating synaptic over-activity, exerts a protective effect, thus promoting neuronal survival and integrity.

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.

Zum Volltext