Cortical spreading depression (CSD)-induced tolerance to transient focal cerebral ischemia in halothane anesthetized rats is affected by anesthetic level but not ATP-sensitive potassium channels

Takashi Horiguchi, Bela Kis, Nishadi Rajapakse, Katsuyoshi Shimizu, David W. Busija

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We investigated the participation of ATP-sensitive potassium (K ATP) channels, adenosine A1 receptors, and the effects of different levels of halothane anesthesia in the development of CSD-induced ischemic tolerance. To elicit CSD, 0.5 M KCl was applied for 2 h to the right hemisphere of halothane anesthetized male Wistar rats. The inhalation concentration of halothane during CSD was maintained at 0.5% (n = 8), 1.0% (n = 8), or 2.0% (n = 8). For control animals, saline was applied instead of KCl (n = 8). To inhibit KATP channels or adenosine A1 receptors, glibenclamide (0.1 mg/kg icv; n = 8), 5-hydroxydeconaoate (5-HD; 100 mg/kg ip; n = 12), or 8-Cyclopentyl-1, 3-dipropylxanthine (DPCPX) (1.0 mg/kg ip; n = 8) was applied before preconditioning during 1.0% halothane anesthesia. Temporary occlusion (120 min) of the right middle cerebral artery was induced 4 days after preconditioning and the infarct volume was measured. Preconditioning elicited under 1.0% halothane reduced cortical infarct volume from 277 ± 15 mm3 in the control group to 159 ± 14 mm3 in the CSD group (mean ± SEM, P < 0.05). In contrast, CSD induced during inhalation of 0.5% or 2.0% halothane did not confer ischemic tolerance. The reduction in infarct area with CSD during inhalation of 1% halothane was not changed in animals treated with glibenclamide or 5-HD or DPCPX. These results uncover a crucial role of halothane level but not of KATP channels or adenosine A1 receptors in the preconditioning effects of CSD.

Original languageEnglish
Pages (from-to)127-133
Number of pages7
JournalBrain Research
Issue number1-2
Publication statusPublished - 2005 Nov 16



  • ATP-sensitive potassium channel
  • Adenosine receptor
  • Cerebral cortex
  • Nitric oxide
  • Preconditioning
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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