Isoflurane reduces septic neuron injury by HO‑1‑mediated abatement of inflammation and apoptosis.

Sepsis‑associated encephalopathy (SAE) frequently occurs in critically ill patients with severe systemic infections. Subanesthetic isoflurane (0.7% ISO) possesses anti‑inflammatory, antioxidant and anti‑apoptotic properties against a number of human diseases, including brain injury. The activation of heme oxygenase‑1 (HO‑1) impedes inflammation, oxidation and apoptosis, thus alleviating sepsis‑induced brain damage. However, whether 0.7% ISO affords protection against septic neuronal injury involving HO‑1 activation is unclear. The present study aimed to investigate the neuroprotective effects of 0.7% ISO and its potential underlying mechanisms in SAE using a mouse model established by cecal ligation and puncture (CLP). The results indicated that the expression and activity of HO‑1 in the mouse hippocampus were increased by CLP, and further enhanced by ISO. ISO reduced the death rate, brain water content and blood‑brain barrier disruption, but improved the learning and memory functions of CLP‑treated mice. ISO significantly decreased the production of pro‑inflammatory cytokines and the levels of oxidative indictors in the serum and hippocampus, as well as the number of apoptotic neurons and the expression of pro‑apoptotic proteins in the hippocampus. Inversely, anti‑inflammatory factors, antioxidative enzymes and anti‑apoptotic proteins were markedly increased by ISO administration. However, the neuroprotective effects of ISO were abolished by a HO‑1 inhibitor. Overall, these findings suggested that 0.7% ISO alleviated SAE via its anti‑inflammatory, antioxidative and anti‑apoptotic properties, which involved the activated form of HO‑1.