title: 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 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 K(ATP) channels or adenosine A1 receptors in the preconditioning effects of CSD.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Horiguchi
authors.forename: Bela
authors.initials: B
authors.lastname: Kis
authors.forename: Nishadi
authors.initials: N
authors.lastname: Rajapakse
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Shimizu
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000502:physiology; D058916:Adenosine A1 Receptor Antagonists; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000008:administration & dosage*; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000502:physiology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D058916:Adenosine A1 Receptor Antagonists; D018685:Anesthetics, Inhalation; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D043682:Receptor, Adenosine A1; D006221:Halothane