Etanercept, an inhibitor of TNF-a, prevents propofol-induced neurotoxicity in the developing brain

Propofol can induce acute neuronal apoptosis, neuronal loss or long-term cognitive impairment when exposed in neonatal rodents, but the mechanisms by which propofol induces developmental neurotoxicity are unclear. Recent studies have demonstrated that propofol can increase the TNF-alpha level in the developing brain, but there is a lack of direct evidence to show whether TNF-alpha is partially or fully involved in propofol-induced neurotoxicity. The present study shows that propofol exposure in neonatal rats induces an increase of TNF-alpha in the cerebral spinal fluid, hippocampus and prefrontal cortex (PFC). Etanercept, a TNF-alpha inhibitor, prevents propofol-induced short- or long-term neuronal apoptosis, neuronal loss, synaptic loss and long-term cognitive impairment. Furthermore, mTNF-alpha (precursor of TNF-alpha) expression in microglia cells is increased after propofol anaesthesia in either the hippocampus or PFC, but mTNF-alpha expression in neurons is only increased in the PFC. These findings suggest that TNF-alpha may mediate propofol-induced developmental neurotoxicity, and etanercept can provide neural protection. Microglia are the main cellular source of TNF-alpha after propofol exposure, while the synthesis of TNF-alpha in neurons is brain-region selective. (C) 2016 ISDN. Published by Elsevier Ltd. All rights reserved.