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

Abstract

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 K ATP 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 mm 3 in the control group to 159 ± 14 mm 3 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 K ATP channels or adenosine A1 receptors in the preconditioning effects of CSD.