Postconditioning with isoflurane reduced ischemia-induced brain injury in rats.

Preexposure of brain to isoflurane, a commonly used anesthetic, induces ischemic tolerance. This phenomenon is called isoflurane preconditioning. However, it is not known whether isoflurane application after ischemia provides neuroprotection.
Corticostriatal slices (400 microm) freshly prepared from adult male Sprague-Dawley rats were subjected to a 15-min oxygen-glucose deprivation (OGD; to simulate ischemia in vitro). Isoflurane was applied after OGD. Brain slices were harvested 2 h after OGD for measuring 2,3,5-triphenyltetrazolium chloride (TTC) conversion to quantify cell injury. Adult male Sprague-Dawley rats were also subjected to middle cerebral arterial occlusion for 90 min and then treated with or without 2% isoflurane for 60 min started at the onset of reperfusion. The infarct volumes, neurologic deficit scores, and performance on rotarod were evaluated at 24 h after the onset of reperfusion.
Isoflurane applied immediately after the 15-min OGD for 30 min dose-dependently reversed the OGD-induced decrease of TTC conversion. The TTC conversion was 34 +/- 16% and 58 +/- 28% of the control, respectively, for OGD alone and OGD plus 2% isoflurane (P < 0.05, n = 12). Application of 2% isoflurane for 30 min started at 10 min after the OGD also reduced the OGD-decreased TTC conversion. The presence of 0.3 microm glibenclamide, a general adenosine 5'-triphosphate-sensitive potassium channel blocker, or 500 microm 5-hydroxydecanoic acid, a mitochondrial adenosine 5'-triphosphate-sensitive potassium channel blocker, during the application of 2% isoflurane abolished the isoflurane preservation of TTC conversion. Application of isoflurane during reperfusion also improved neurologic outcome after brain ischemia.
The results suggest that isoflurane administrated after OGD or brain ischemia provides neuroprotection. Mitochondrial adenosine 5'-triphosphate-sensitive potassium channels may be involved in this protection.
AuthorsJeong Jin Lee, Liaoliao Li, Hae-Hyuk Jung, Zhiyi Zuo
JournalAnesthesiology (Anesthesiology) Vol. 108 Issue 6 Pg. 1055-62 (Jun 2008) ISSN: 1528-1175 [Electronic] United States
PMID18497606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anesthetics, Inhalation
  • Decanoic Acids
  • Hydroxy Acids
  • Neuroprotective Agents
  • Potassium Channel Blockers
  • Tetrazolium Salts
  • 5-hydroxydecanoic acid
  • triphenyltetrazolium
  • Isoflurane
  • Glyburide
  • Anesthetics, Inhalation (pharmacology)
  • Animals
  • Brain (blood supply, drug effects)
  • Decanoic Acids (pharmacology)
  • Dose-Response Relationship, Drug
  • Glyburide (pharmacology)
  • Hydroxy Acids (pharmacology)
  • Hypoxia-Ischemia, Brain (etiology, pathology, prevention & control)
  • Infarction, Middle Cerebral Artery (complications)
  • Isoflurane (pharmacology)
  • Male
  • Middle Cerebral Artery (drug effects)
  • Neuroprotective Agents (pharmacology)
  • Organ Culture Techniques
  • Potassium Channel Blockers (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (prevention & control)
  • Tetrazolium Salts (metabolism, pharmacokinetics)

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