Isoflurane reduces septic neuron injury by HO­1­mediated abatement of inflammation and apoptosis.

Sepsis­associated encephalopathy (SAE) frequently occurs in critically ill patients with severe systemic infections. Subanesthetic isoflurane (0.7% ISO) possesses anti­inflammatory, antioxidant and anti­apoptotic properties against a number of human diseases, including brain injury. The activation of heme oxygenase­1 (HO­1) impedes inflammation, oxidation and apoptosis, thus alleviating sepsis­induced brain damage. However, whether 0.7% ISO affords protection against septic neuronal injury involving HO­1 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 HO­1 in the mouse hippocampus were increased by CLP, and further enhanced by ISO. ISO reduced the death rate, brain water content and blood­brain barrier disruption, but improved the learning and memory functions of CLP­treated mice. ISO significantly decreased the production of pro­inflammatory cytokines and the levels of oxidative indictors in the serum and hippocampus, as well as the number of apoptotic neurons and the expression of pro­apoptotic proteins in the hippocampus. Inversely, anti­inflammatory factors, antioxidative enzymes and anti­apoptotic proteins were markedly increased by ISO administration. However, the neuroprotective effects of ISO were abolished by a HO­1 inhibitor. Overall, these findings suggested that 0.7% ISO alleviated SAE via its anti­inflammatory, antioxidative and anti­apoptotic properties, which involved the activated form of HO­1.