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Anesth Analg. 2011 Jul;113(1):153-9. doi: 10.1213/ANE.0b013e31821a9fbe. Epub 2011 Apr 27.

Reactive oxygen species scavenger inhibits STAT3 activation after transient focal cerebral ischemia-reperfusion injury in rats.

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1
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.

Abstract

BACKGROUND:

Signal transducer and activator of transcription 3 (STAT3) activation in ischemic brain has been verified. However, the mechanism and the role of STAT3 activation after cerebral ischemia-reperfusion are poorly elucidated. In the present study, we sought to test the hypothesis that STAT3 activation after cerebral ischemia-reperfusion was related to reactive oxygen species (ROS) production.

METHODS:

Adult male Sprague-Dawley rats were subjected to focal cerebral ischemia induced by middle cerebral artery occlusion. STAT3 activation was evaluated by immunohistochemistry and Western blotting. Rats were subjected to permanent ischemia or ischemia-reperfusion to clarify the temporal profile of STAT3 activation. The role of ROS in inducing STAT3 activation was assessed by administration of the ROS scavenger dimethylthiourea (DMTU). The effects of DMTU and the STAT3 activation inhibitor AG490 administration on brain ischemic injuries were evaluated by neurologic behavior scores and brain infarct volumes.

RESULTS:

The activation of STAT3 after middle cerebral artery occlusion was significantly increased within peri-ischemia neurons and astrocytes. STAT3 activation mainly occurred in the reperfusion phase rather than in the ischemia phase. In addition, DMTU suppressed STAT3 activation in a dose-dependent manner, indicating that STAT3 activation may be a subsequent event after ROS production. DMTU and AG490 significantly reduced infarct sizes and improved neurologic outcomes.

CONCLUSION:

In comparison with ischemia, reperfusion is a more powerful stimulus for STAT3 activation. ROS scavenging is closely correlated with an inhibition of STAT3 activation. Neuroprotective effects are achieved through ROS scavenging and down-regulation of STAT3 activation.

PMID:
21525184
DOI:
10.1213/ANE.0b013e31821a9fbe
[Indexed for MEDLINE]
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