Advances in precision anaesthesia may be found by testing our resistance to change

Abstract

IL-17A promotes the neuroinflammation and cognitive function in sevoflurane anesthetized aged rats via activation of NF-kB signaling pathway.

The Inert Brain: Explaining Neural Inertia as Post-anaesthetic Sleep Inertia

“…This is precisely what is observed empirically, with higher neural inertia in previously sleep-deprived animals (Joiner et al, 2013). Moreover, this hypothesis could explain why Friedman and colleagues (Friedman et al, 2010) observed greater neural inertia with halothane than with isoflurane-a result that was recently replicated in mice exposed to equipotent doses of isoflurane, sevoflurane, and halothane, demonstrating that different anaesthetics have different effects on neural inertia, distinct from their potency (Wasilczuk et al, 2020). Specifically, to explain these results we note that unlike isoflurane, halothane does not reduce NREM sleep-debt in rodents (Pick et al, 2011;Scharf and Kelz, 2013).…”

“…While some authors (Colin et al, 2018) criticised this study by arguing that the hysteresis observed by Warnaby and colleagues can be collapsed if a different effectsite equilibration model is assumed, recent modelling work by Proekt and Kelz (2020) demonstrated that-since effect-site concentration is a theoretical construct that cannot be measured directly-it is experimentally impossible to distinguish between an equilibration model that collapses hysteresis and one that does not, even when hysteresis is in part attributable to genuine neuronal dynamics. Therefore, although it is clear that improved methodologies will be required (Proekt and Kelz, 2020), there is reason to believe that humans may also be subject to neural inertia-a postulation consistent with the unequivocal evidence that neural inertia is a widespread phenomenon observed in species as diverse as fruit flies, zebrafish, and rodents (Sepúlveda et al, 2019;Wasilczuk et al, 2020). As Proekt and Kelz observe: "whereas going from the structured to the unstructured state is trivial, the restoration of structure is not generically expected after a dramatic perturbation" (Proekt and Kelz, 2020).…”

“…Indeed, implication of orexin and noradrenaline in neural inertia has been considered before (Sepúlveda et al, 2019;Wasilczuk et al, 2020). Wasilczuk et al (2020) observed that halothane does not suppress hypothalamic orexinergic neurons and LC noradrenergic neurons (Gompf et al, 2009), whereas isoflurane does suppress them (Kelz et al, 2008). Thus, these authors proposed that this difference may underlie the increased neural inertia induced by halothane compared with isoflurane (Friedman et al, 2010;Wasilczuk et al, 2020) due to non-abolished orexinergic activity.…”

“…Testing this prediction in humans is not straightforward, for the same reason that complicates existing attempts to identify neural inertia in humans (Sepúlveda et al, 2019): namely Proekt and Kelz (2020) demonstrated that since effect-site concentration cannot be measured directly, effect-site models could be constructed to collapse hysteresis even when it would actually be attributable to genuine neuronal dynamics. However, the hypothesis is not specific to humans and could be tested in other species for which neural inertia has already been demonstrated with other anaesthetics (Friedman et al, 2010;Joiner et al, 2013;McKinstry-Wu et al, 2019;Wasilczuk et al, 2020), with the prediction being that little hysteresis should be observed. Additionally, we reported above that if neural inertia is due to the increased susceptibility to anaesthetics that occurs during postanaesthetic sleep inertia, then our hypothesis predicts that higher susceptibility to anaesthesia should be observed during sleep inertia (e.g., as induced by awakening from slow-wave sleep).…”

“…Indeed, implication of orexin and noradrenaline in neural inertia has been considered before (Sepúlveda et al, 2019;Wasilczuk et al, 2020). Wasilczuk et al (2020) observed that halothane does not suppress hypothalamic orexinergic neurons and LC noradrenergic neurons (Gompf et al, 2009), whereas isoflurane does suppress them (Kelz et al, 2008).…”