Palladium–reduced graphene oxide nanocomposites enhance neurite outgrowth and protect neurons from Ishemic stroke

Abstract

Currently, the construction of novel biomimetic reduced graphene oxide (RGO)-based nanocomposites to induce neurite sprouting and repair the injured neurons represents a promising strategy in promoting neuronal development or treatment of cerebral anoxia or ischemia. Here, we present an effective method for constructing palladium-reduced graphene oxide (Pd-RGO) nanocomposites by covalently bonding Pd onto RGO surfaces to enhance neurite sprouting of cultured neurons. As described, the Pd-RGO nanocomposites exhibit the required physicochemical features for better biocompatibility without impacting cell viability. Primary neurons cultured on Pd-RGO nanocomposites had significantly increased number and length of neuronal processes, including both axons and dendrites, compared with the control. Western blotting showed that Pd-RGO nanocomposites improved the expression levels of growth associate protein-43 (GAP-43), as well as β-III tubulin, Tau-1, microtubule-associated protein-2 (MAP2), four proteins that are involved in regulating neurite sprouting and outgrowth. Importantly, Pd-RGO significantly promoted neurite length and complexity under oxygen-glucose deprivation/re-oxygenation (OGD/R) conditions, an in vitro cellular model of ischemic brain damage, that closely relates to neuronal GAP-43 expression. Furthermore, using the middle cerebral artery occlusion (MCAO) model in rats, we found Pd-RGO effectively reduced the infarct area, decreased neuronal apoptosis in the brain, and improved the rats’ behavioral outcomes after MCAO. Together, these results indicate the great potential of Pd-RGO nanocomposites as a novel excellent biomimetic material for neural interfacing that shed light on its applications in brain injuries.

Keywords

• Pd-RGO
• Neurite
• Sprouting
• Outgrowth
• OGD/R
• Ischemia/reperfusion