title: The effect of ketamine on optical and electrical characteristics of spreading depolarizations in gyrencephalic swine cortex.
abstract: Spreading depolarization (SD) is a wave of mass neuronal and glial depolarization that propagates across the cerebral cortex and has been implicated in the pathophysiology of brain injury states and migraine with aura. Analgesics and sedatives seem to have a significant effect on SD modulation. Studies have shown that ketamine, an NMDA receptor blocker, has the capacity to influence SD occurrence. The aim of this study was to analyze the dose-dependent effect of ketamine on SD susceptibility through electrocorticography (ECoG) and intrinsic optical signal (IOS) imaging in a gyrencephalic brain. Ketamine in a low-dose infusion (2 mg/kg/h) decreases SD spread and had an effect on the amplitude of SD deflections, as well as on duration, and speed. Moreover, during ketamine infusion at this dose, there was a sustained decrease in the hyperemic response following SD. However, a high-dose infusion (4 mg/kg/h) of ketamine inhibited SD induction and expansion. Furthermore, a high-dose bolus (4 mg/kg), 1 min after stimulation, blocked SD propagation abruptly within 1-2 min, and hindered SD induction and expansion for the following 15-30 min. The results suggest that ketamine may be therapeutically beneficial in preventing SDs. Nonetheless, an adequate dosage and way of administration should be considered and established for human use.
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: renan.sanchez-porras@med.uni-heidelberg.de.
authors.forename: Renán
authors.initials: R
authors.lastname: Sánchez-Porras
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Santos
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany; Institute of Medical Biometry and Informatics, Ruprecht Karls University, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schöll
authors.affiliation: Institute of Medical Biometry and Informatics, Ruprecht Karls University, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stock
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Zelong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schiebel
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Berk
authors.initials: B
authors.lastname: Orakcioglu
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Unterberg
authors.affiliation: Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Sakowitz
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006940:Hyperemia / Q000188:drug therapy / Q000503:physiopathology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D061848:Optical Imaging; D013552:Swine; D013997:Time Factors; D014741:Video Recording
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
keywords: Electrocorticography (ECoG); Intrinsic optical signal (IOS) imaging; Ketamine; NMDA receptor blocker; Spreading depolarization (SD)