Preclinical assessment of ketamine

Abstract

Ketamine is used as a general anesthetic, and recent data suggest that anesthetics can cause neurodegeneration and/or neuroprotection. The precise mechanisms are not completely understood. This review is to examine the work on ketamine and to address how developmental biology may be utilized when combined with biochemical, pathological, and pharmacokinetic assessments to produce a bridging model that may decrease the uncertainty in extrapolating preclinical data to human conditions. Advantages of using preclinical models to study critical issues related to ketamine anesthesia have been described. These include the relationships between ketamine-induced neurotoxicity/protection and the preclinical models/approaches in elucidating mechanisms associated with ketamine exposure. The discussions focus on the following: (1) the doses and time-course over which ketamine is associated with damage to, or protection of, neural cells, (2) how ketamine directs or signals neural cells to undergo apoptosis or necrosis, (3) how such exposures can trigger mitochondrial dysfunction, (4) how antioxidants and knockdowns of specific transcription modulators or receptors affect neurotoxicity induced by ketamine, and (5) whether the potential neural damage can be monitored after ketamine exposure in living animals using positron emission tomography.