The effect of ketamine on optical and electrical characteristics of spreading depolarizations in gyrencephalic swine cortex

• Published in: Neuropharmacology 2014-09, Vol.84, p.52-61
• Main Authors: Sánchez-Porras, Renán, Santos, Edgar, Schöll, Michael, Stock, Christian, Zheng, Zelong, Schiebel, Patrick, Orakcioglu, Berk, Unterberg, Andreas W., Sakowitz, Oliver W.
• Format: Article
• Language: English
• Subjects: Animals; Cerebral Cortex - drug effects; Cerebral Cortex - physiopathology; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Cortical Spreading Depression - drug effects; Cortical Spreading Depression - physiology; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocorticography (ECoG); Electroencephalography; Excitatory Amino Acid Antagonists - pharmacology; Hyperemia - drug therapy; Hyperemia - physiopathology; Intrinsic optical signal (IOS) imaging; Ketamine; Ketamine - pharmacology; Male; NMDA receptor blocker; Optical Imaging; Spreading depolarization (SD); Swine; Time Factors
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2014.04.018

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. •Ketamine at a therapeutic dosage can modulate SD in the gyrencephalic brain.•A ketamine bolus (4 mg/kg) can block SD propagation abruptly.•Ketamine infusions at 2 mg/kg/h and 4 mg/kg/h can suppress SDs in clusters.•Ketamine has an effect on the hemodynamic response to SD.