Chronic mild stress (CMS) in mice: of anhedonia, 'anomalous anxiolysis' and activity.

BACKGROUND: In a substantial proportion of depressed patients, stressful life events play a role in triggering the evolution of the illness. Exposure to stress has effects on different levels in laboratory animals as well and for the rat it has been shown that chronic mild stress (CMS) can cause antidepressant-reversible depressive-like effects. The adoption of the model to the mouse seems to be problematic, depending on the strain used and behavioural endpoint defined. Our aim was to evaluate the applicability of CMS to mice in order to induce behavioural alterations suggested to reflect depression-like symptoms. METHODOLOGY/PRINCIPAL FINDINGS: A weekly CMS protocol was applied to male mice of different mouse strains (D2Ola, BL/6J and BL/6N) and its impact on stress-sensitive behavioural measures (anhedonia-, anxiety- and depression-related parameters) and body weight was assessed. Overnight illumination as commonly used stressor in CMS protocols was particularly investigated in terms of its effect on general activity and subsequently derived saccharin intake. CMS application yielded strain-dependent behavioural and physiological responses including 'paradox' anxiolytic-like effects. Overnight illumination was found to be sufficient to mimic anhedonic-like behaviour in BL/6J mice when being applied as sole stressor. CONCLUSIONS/SIGNIFICANCE: The CMS procedure induced some behavioural changes that are compatible with the common expectations, i.e. 'anhedonic' behaviour, but in parallel behavioural alterations were observed which would be described as 'anomalous' (e.g. decreased anxiety). The results suggest that a shift in the pattern of circadian activity has a particular high impact on the anhedonic profile. Changes in activity in response to novelty seem to drive the 'anomalous' behavioural alterations as well

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons