Sevoflurane preconditioning induces brain ischemic tolerance , but the mechanism remains poorly elucidated. A nitration is an important form of post-translational modification in pathological signaling. This study was to investigate the role of thioredoxin-1 (Trx-1) nitration in neuroprotection effect induced by sevoflurane preconditioning in a transient stroke model in rats.

Preconditioning with volatile anesthetics induces tolerance to cerebral ischemia / reperfusion injury in animals, and prevents neurological complications such as perioperative stroke in patients Sevoflurane, one of the popular inhalational anesthetics, has shown the neuroprotective property in perioperative period. However, the mechanism of sevoflurane preconditioning is not fully understood.

Adult male Sprague-Dawley rats were preconditioned with 2% sevoflurane or vehicle oxygen exposure, 1 h per day, for 5 consecutive days. At 24 h after the last exposure, rats were subjected to focal brain ischemia induced by middle cerebral artery occlusion (MCAO) for 90 min, followed by 72-h reperfusion.

Trx-1 expression and activity, as well as the content of nitrotyrosine at penumbra were detected at 24 h after preconditioning and 2, 8, 24, 72 h after MCAO. Nitrated Trx-1 was examined by immunoprecipitation at 8 h after MCAO. The role of Trx-1 nitration in ischemic tolerance was assessed by administration of nitrated human-Trx-1 prior to MCAO. Neurological scores, brain infarct volumes and TUNEL staining were evaluated at 24 h after reperfusion.


Ischemic stroke decreased Trx-1 activity but not the expression in penumbra tissue. The content of nitrotyrosine was elevated after MCAO. Preconditioning with sevoflurane increased Trx-1 activity and reduced its nitration at 8 h after MCAO in comparison with vehicle preconditioning.

The decrement of Trx-1 activity was correlated with its nitration level . Exogenous administration of nitrated human-Trx-1 reversed the brain ischemic tolerance of sevoflurane preconditioning, exacerbating brain infarct volume, neurobehavioral defects and apoptosis, while administration of human-Trx-1 had no effect on the sevoflurane preconditioning-induced neuroprotection .

Trx-1 activity

Ischemic stroke reduces Trx-1 activity via post-translational nitrative modulation in rats. Sevoflurane preconditioning induces brain ischemic tolerance and anti-apoptosis by partially preserving Trx-1 activity via inhibiting nitration.

Since we used exactly the same protocol for preconditioning as our previous studies the physiologic variables at the end of the last preconditioning exposure and during surgery had been reported. Briefly, no difference in pH value, temporal temperature (T ° C), partial pressure of oxygen (PaO 2 ) and partial pressure of carbon dioxide (PaCO 2 ) were observed between sevoflurane preconditioning and its vehicle oxygen groups.