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.