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Isoflurane postconditioning reduces ischemia-induced nuclear factor-κB activation and interleukin 1β production to provide neuroprotection in rats and mice.

Abstract
Application of isoflurane, a volatile anesthetic, after brain ischemia can reduce ischemic brain injury in rodents (isoflurane postconditioning). This study is designed to determine whether isoflurane postconditioning improves long-term neurological outcome after focal brain ischemia and whether this protection is mediated by attenuating neuroinflammation. Adult male Sprague-Dawley rats were subjected to a 90-min middle cerebral arterial occlusion (MCAO). Isoflurane postconditioning was performed by exposing rats to 2% isoflurane for 60min immediately after the MCAO. Isoflurane postconditioning reduced brain infarct volumes, apoptotic cells in the ischemic penumbral brain tissues and neurological deficits of rats at 4weeks after the MCAO. Isoflurane postconditioning reduced brain ischemia/reperfusion-induced nuclear transcription factor (NF)-κB (NF-κB) activation as well as interleukin 1β (IL-1β) and interleukin-6 production in the ischemic penumbral brain tissues at 24h after the MCAO. IL-1β deficient mice had smaller brain infarct volumes and better neurological functions than wild-type mice at 24h after a 90-min focal brain ischemia. Isoflurane posttreatment failed to induce neuroprotection in the IL-1β deficient mice. Our results suggest that isoflurane postconditioning improved long-term neurological outcome after transient focal brain ischemia. This protection may be mediated by inhibiting NF-κB activation and the production of the proinflammatory cytokine IL-1β.
AuthorsHong Li, Jinbo Yin, Liaoliao Li, Jiao Deng, Chenzhuo Feng, Zhiyi Zuo
JournalNeurobiology of disease (Neurobiol Dis) Vol. 54 Pg. 216-24 (Jun 2013) ISSN: 1095-953X [Electronic] United States
PMID23313315 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Interleukin-1beta
  • NF-kappa B
  • Neuroprotective Agents
  • Isoflurane
Topics
  • Animals
  • Blotting, Western
  • Brain Ischemia (metabolism, pathology)
  • Enzyme-Linked Immunosorbent Assay
  • In Situ Nick-End Labeling
  • Interleukin-1beta (biosynthesis)
  • Ischemic Postconditioning (methods)
  • Isoflurane (pharmacology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B (metabolism)
  • Neuroprotective Agents (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function (drug effects)

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