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

Author:

Tortella Lorenza1ORCID,Santini Irene1ORCID,Lozano Neus2ORCID,Kostarelos Kostas23ORCID,Cellot Giada1ORCID,Ballerini Laura1ORCID

Affiliation:

1. Neuroscience Area International School for Advanced Studies (SISSA/ISAS) Via Bonomea 265 34136 Trieste Italy

2. Catalan Institute of Nanoscience and Nanotechnology (ICN2) CSIC and BIST Campus UAB Bellaterra 08193 Barcelona Spain

3. Nanomedicine Lab and Faculty of Biology Medicine & Health The National Graphene Institute University of Manchester Manchester M13 9PL United Kingdom

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.

Funder

HORIZON EUROPE European Innovation Council

Publisher

Wiley

Subject

General Chemistry,Catalysis,Organic Chemistry

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