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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Jeong Jin Lee, Liaoliao Li, Hae-Hyuk Jung, Zhiyi Zuo
• Journal: Anesthesiology (Anesthesiology) Vol. 108 Issue 6 Pg. 1055-62 (Jun 2008) ISSN: 1528-1175 [Electronic] United States
• PMID: 18497606 (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

Topics

• 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)