There is developing interest in the potential association between anesthesia and the onset and progression of Alzheimer's disease. Several anesthetics have thus been demonstrated to induce tau hyperphosphorylation, an effect mostly mediated by anesthesia-induced hypothermia. Here, we tested the hypothesis that acute normothermic administration of dexmedetomidine, an intravenous sedative used in intensive care units, would result in tau hyperphosphorylation in vivo and in vitro. When administered to non-transgenic mice, dexmedetomidine induced tau hyperphosphorylation persisting up to 6h in the hippocampus for the AT8 epitope. Pretreatment with atipamezole, a highly specific α2-adrenergic receptor (α2-AR) antagonist, blocked dexmedetomidine-induced tau hyperphosphorylation. Furthermore, dexmedetomidine dose-dependently increased tau phosphorylation at AT8 in SH-SY5Y cells, impaired mice spatial memory in the Barnes maze, and promoted tau hyperphosphorylation and aggregation in transgenic hTau mice. These findings suggest that dexmedetomidine: i) increases tau phosphorylation, in vivo and in vitro, in the absence of anesthetic-induced hypothermia and through α2-AR activation, ii) promotes tau aggregation in a mouse model of tauopathy, and iii) impacts spatial reference memory.

ObjectiveTo describe how small animal anaesthesia is performed in French-speaking Eastern Canada, and the variations between practices, in particular based on practice type, veterinarian gender and experience. DesignObservational study, survey. Sample 156 respondents. ProcedureA questionnaire was designed to assess current small animal anaesthesia practices in French-speaking Eastern Canada, mainly in the province of Quebec. The questionnaire was available through SurveyMonkey, and consisted of four parts: demographic information about the veterinarians surveyed, evaluation and management of anaesthetic risk, anaesthesia procedure, monitoring and safety. Gender, year of graduation, and type of practice were tested as potential risk factors. Chi-square exact test was used to study relations between each risk factor, and the effect of the selected risk factor on each response of the survey. For ordinal data, the Cochran-Mantel-Haenszel test was used to maximize power. ResultsResponse rate over a period of 3 months was 20.85% (156 respondents). Overall, the way anaesthesia is performed by most respondents does not meet international guidelines, such as patient preparation and evaluation prior to anaesthesia, not using individualised protocols (for 41%), not obtaining intravenous access (12.4% use it for all their anaesthesia in cats, and 30.6% in dogs), lack of patient monitoring at certain intervals for 55% of the responses, PLOS ONE | https://doi.org/10.1371/journal.pone.

Summary Background There is no information directly comparing midazolam with guaifenesin when used in combination with an alpha‐2 agonist and ketamine to maintain anaesthesia via i.v. infusion in horses. Objectives To compare ketamine–medetomidine–guaifenesin with ketamine–medetomidine–midazolam for total intravenous anaesthesia (TIVA) in young horses anaesthetised for computerised tomography. Study design Prospective, randomised, blinded, crossover trial. Methods Fourteen weanlings received medetomidine 7 μg/kg bwt i.v. and anaesthesia was induced with ketamine 2.2 mg/kg bwt i.v. On two separate occasions horses each received infusions of ketamine 3 mg/kg bwt/h, medetomidine 5 μg/kg bwt/h, guaifenesin 100 mg/kg bwt/h (KMG) or ketamine 3 mg/kg bwt/h, medetomidine 5 μg/kg bwt/h, midazolam 0.1 mg/kg bwt/h (KMM) for 50 min. Cardiorespiratory variables and anaesthetic depth were assessed every 5–10 min. Recovery times after the infusions ceased were recorded and recovery quality was assessed using a composite score system (CSS), simple descriptive scale (SDS) and visual analogue scale (VAS). Multivariable models were used to generate mean recovery scores for each treatment and each recovery score system and provide P‐values comparing treatment groups. Results Anaesthesia was uneventful with no difference in additional anaesthetic requirements and little clinically relevant differences in cardiopulmonary variables between groups. All horses recovered without incident with no significant difference in recovery times. Quality of the anaesthetic recovery was significantly better for the KMM group compared with the KMG group using the CSS (P<0.001), SDS (P<0.001) and VAS (P<0.001). Main limitations No surgical stimulus was applied and study animals may not represent general horse population. Conclusion Midazolam is a suitable alternative to guaifenesin when co‐infused with ketamine and medetomidine for anaesthesia in young horses undergoing noninvasive procedures. Both infusions produce a clinically comparable quality of anaesthesia; however, recovery from anaesthesia is of a better quality following an infusion of ketamine–medetomidine–midazolam.

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