General anesthesia-induced pharmacological protection of the central nervous system following injury has been under intense investigations during the past four decades. Indeed, if
general anesthetics could provide therapeutic benefit in the event of
hypoxia,
ischemia or any other kinds of brain lesions, that would be of tremendous clinical importance. The potential for
anesthesia-related brain protection, however, has been seriously challenged during the past 10 years. In fact, an increasing number of experimental and, more recently, clinical observations suggest that
general anesthetics might exert unwanted, toxic effects on the brain especially when administered to young infants or to the elderly. Of utmost importance, recent data suggest that these same drugs could even have
therapeutic effects in some
psychiatric disorders. The goal of this review is to highlight these apparent contradictions. We will consider the available experimental evidence arguing for
anesthetic-induced neuroprotection and highlight the lack of clinical studies supporting this notion. The
biological rational for
anesthesia neurotoxicity will then be explored together with existing experimental and clinical evidence in favor of this possibility. Finally, insights into the increasing number of both experimental and clinical data suggesting that
general anesthetics, especially
ketamine, support the therapeutic value of these drugs in
major depressive disorders. When taken together, these seemingly contradictory observations suggest the intriguing possibility that
general anesthetics could stand as valuable context-dependent modulators of neural plasticity.