The role of general anesthetics and the mechanisms of hippocampal and extra-hippocampal dysfunctions in the genesis of postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a multifactorial process with a huge number of predisposing, causal, and precipitating factors. In this scenario, the neuroinflammation and the microglial activation play a pivotal role by triggering and amplifying a complex cascade involving the immuno-hormonal activation, the micro circle alterations, the hippocampal oxidative stress activation and, finally, an increased blood-brain barrier's permeability. While the role of anesthetics in the POCD's genesis in humans is debated, a huge number of preclinical studies have been conducted on the topic and many mechanisms have been proposed to explain the potential neurodegenerative effects of general anesthetics. Probably, the problem concerns on what we are searching for and how we are searching and, surprisingly, preclinical studies showed that anesthetics may also manifest neuroprotective properties. The aim of this paper is to offer an overview on the potential impact of general anesthetics on POCD. Mechanisms of hippocampal and extra-hippocampal dysfunction due to neuroinflammation are discussed, whereas further research perspectives are also given.