TAK‑242 exerts a neuroprotective effect via suppression of the TLR4/MyD88/TRIF/NF‑κB signaling pathway in a neonatal hypoxic‑ischemic encephalopathy rat model.

Abstract

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the main causes of death and nervous system damage in neonates. The aim of the present study was to investigate the effect of the Toll-like receptor 4 (TLR4) antagonist TAK-242 on HIE. The Rice-Vannucci method was used for ligation of the left common carotid artery, followed by hypoxic treatment for 2.5 h to establish a neonatal HIE rat model. Rats were intraperitoneally injected with 7.5 ml/kg TAK-242 after hypoxia-ischemia. It was demonstrated that TAK-242 significantly reduced the infarct volume and cerebral edema content of neonatal rats after HIE, alleviating neuronal damage and neurobehavioral function deficits. Furthermore, TAK-242 decreased the protein expression levels of TLR4, MyD88, TIR-domain-containing adapter-inducing interferon-β (TRIF), NF-κB, tumor necrosis factor α (TNF-α) and interleukin-1β in the hippocampus. The present results suggested that TAK-242 may exert a neuroprotective effect after HIE by inhibiting the TLR4/MyD88/TRIF/NF-κB signaling pathway, and reducing the release of downstream inflammatory cytokines.