Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives DOI Creative Commons
Dongdong Zang, Xuemei Yang, Hao Wang

et al.

Clinics, Journal Year: 2024, Volume and Issue: 79, P. 100435 - 100435

Published: Jan. 1, 2024

This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. Four HNK were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization conditioned location preference test used to screen the activity of synthesized target compounds. In case 10 mg treatment, compared with saline, immobile time mice in group, I5 group I6 at 1 h 7 days had statistical significance. compound C D groups glass cylinder area was significantly different. movement distance on day 15 increased first day. place experiment, induced Veh group. The results forced showed that may have certain anti-depressant activity. However, exerts a rapid significant effect within week, but duration is short.

Language: Английский

Local orchestration of distributed functional patterns supporting loss and restoration of consciousness in the primate brain DOI Creative Commons
Andrea I. Luppi, Lynn Uhrig, Jordy Tasserie

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 11, 2024

Abstract A central challenge of neuroscience is to elucidate how brain function supports consciousness. Here, we combine the specificity focal deep stimulation with fMRI coverage entire cortex, in awake and anaesthetised non-human primates. During propofol, sevoflurane, or ketamine anaesthesia, subsequent restoration responsiveness by electrical thalamus, investigate loss consciousness impacts distributed patterns structure-function organisation across scales. We report that activity under anaesthesia increasingly constrained structure scales, coinciding anaesthetic-induced collapse multiple dimensions hierarchical cortical organisation. These signatures are observed different anaesthetics, they reversed recovery behavioural markers arousal. No such effects were upon stimulating ventral lateral demonstrating specificity. Overall, identify consistent orchestrated specific thalamic nuclei.

Language: Английский

Citations

13

Influence of clinical and genetic factors on propofol dose requirements: A genome-wide association study DOI Creative Commons
Sirkku Ahlström, Paula Reiterä, R. JOKELA

et al.

Anesthesiology, Journal Year: 2024, Volume and Issue: 141(2), P. 300 - 312

Published: May 3, 2024

Background Propofol is a widely used intravenous hypnotic. Dosing based mostly on weight, with great interindividual variation in consumption. Suggested factors affecting propofol requirements include age, sex, ethnicity, anxiety, alcohol consumption, smoking, and concomitant valproate use. Genetic have not been explored. Methods This study considered 1,000 women undergoing breast cancer surgery under remifentanil anesthesia. Depth of anesthesia was monitored State Entropy (GE Healthcare, Finland). during were recorded. DNA from blood genotyped genome-wide array. A multivariable linear regression model to assess the relevance clinical variables select those be as covariates association study. Imputed genotype data explore selected loci further. In silico functional annotation possible consequences discovered genetic variants. Additionally, previously reported associations candidate gene studies tested. Results Body mass index, smoking status, use, dose (ln[mg · kg−1 min−1]), average remained statistically significant model. Two reached significance (P < 5 × 10−8). The most for single-nucleotide polymorphisms rs997989 (30 kb ROBO3), likely expression another nearby gene, FEZ1, rs9518419, close NALCN (sodium leak channel); rs10512538 near KCNJ2 encoding Kir2.1 potassium channel showed suggestive = 4.7 10−7). None these are coding variants but possibly affect regulation genes. pharmacokinetics or pharmacodynamics data. Conclusions this first exploring requirements, novel suggesting new biologically relevant pathways general roles products ROBO3/FEZ1, NALCN, warrant further studies. Editor’s Perspective What We Already Know about Topic Article Tells Us That Is New

Language: Английский

Citations

4

Local Orchestration of Global Functional Patterns Supporting Loss and Restoration of Consciousness in the Primate Brain DOI Creative Commons
Andrea I. Luppi, Lynn Uhrig, Jordy Tasserie

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 3, 2023

Abstract A central challenge of neuroscience is to elucidate how the orchestration brain function modulated by different states consciousness. Here, we investigate link between distributed structural and functional organisation in MRI signals non-human primates, through bi-directional causal manipulations During varying levels propofol, sevoflurane, or ketamine anaesthesia, subsequent restoration responsiveness deep stimulation thalamus, loss consciousness impacts patterns structure-function across scales. Combining specificity electrical with global fMRI coverage entire cortex, report that activity under anaesthesia increasingly constrained structure scales, coinciding anaesthetic-induced collapse multiple dimensions hierarchical cortical organisation. Crucially, show these signatures are observed anaesthetics, they reversed recovery behavioural markers during propofol anaesthesia. No such effects were upon a control anatomical site, ventral lateral demonstrating specificity. Through integrate pharmacology intracranial our results identify local specific nuclei thalamus. Overall, present work broadens understanding network supporting consciousness, interplay architecture.

Language: Английский

Citations

10

Exploring the Impact of Medication Confounders on Determining Death by Neurologic Criteria: An International Survey Investigating Practice Variations DOI Creative Commons
Casey C. May,

Jeffrey Mucksavage,

Christopher N. Morrison

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Abstract Background and Objective: The determination of death by neurologic criteria (DNC) is completed a clinical examination alone if no confounding conditions render the unreliable. Currently, consensus guidelines on DNC state patient should be free any confounders prior to testing; however, how these are reviewed evaluated not specified. This project aimed investigate assessment medication during DNC.Methods: A 28-question survey was developed study team Neurocritical Care Society (NCS) Research Operations Subcommittee. care practitioners who NCS members received invitations participate in an institutional review board (IRB) – exempt, electronic survey.Results: Of 69 respondents survey, most were physicians (48%) or pharmacists (41%), work urban area (94%) at academic medical center (78%). Respondents have neurology admitting service (81%), neurocritical unit (91%), guideline that governs (94%). Out those guideline, 83% require medications majority (89%) do it pharmacist. When asked reviews (select all apply), reported 90% time addition (40%) advanced practice providers (28%). Additionally, when ancillary testing appropriate, recommended present centers (74%). However, drug suspected, only 15% said would pursued ‘always’ 35% ‘frequently’.Conclusion: Most recommends/requires DNC. Variation exists utilized setting responsible patients’ More research essential develop standardized protocols ensure reliable accurate determinations presence confounders.

Language: Английский

Citations

0

Associations between anaesthetic dose-adjusted intraoperative EEG alpha power, processing speed, and postoperative delirium: analysis of data from three prospective studies DOI
Melody Reese, Mary Cooter, Kenneth Roberts

et al.

British Journal of Anaesthesia, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0

Propofol Disrupts the Functional Core-Matrix Architecture of the Thalamus in Humans DOI Creative Commons
Zirui Huang, George A. Mashour, Anthony G. Hudetz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

Abstract Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either thalamus as a whole or focused on specific subregions, overlooking distinct neuronal subtypes like core matrix cells. We conducted study heathy volunteers magnetic resonance imaging during conscious baseline, deep sedation, recovery. advanced gradient mapping technique delineate geometry circuits, within framework unimodal-transmodal axis cortex. observed significant shift this unconsciousness, marked by dominance unimodal over transmodal geometry. This alteration was closely linked spatial variations density cells thalamus. research bridges cellular systems-level understanding, highlighting crucial thalamic core–matrix architecture understanding neural mechanisms states consciousness.

Language: Английский

Citations

2

Propofol disrupts the functional core-matrix architecture of the thalamus in humans DOI Creative Commons
Zirui Huang, George A. Mashour, Anthony G. Hudetz

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 9, 2024

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either thalamus as a whole or focused on specific subregions, overlooking distinct neuronal subtypes like core matrix cells. We conducted study heathy volunteers magnetic resonance imaging during conscious baseline, deep sedation, recovery. advanced gradient mapping technique delineate geometry circuits, within framework unimodal-transmodal axis cortex. Here we show significant shift this marked by transmodal-deficient geometry. This alteration closely linked spatial variations cell composition thalamus. research bridges cellular systems-level understanding, highlighting crucial thalamic core-matrix architecture understanding neural mechanisms states consciousness.

Language: Английский

Citations

2

SESN2 attenuates sevoflurane-induced cognitive impairment and neuroinflammation in rats DOI
Li Sun,

Yangyang Li,

Daliang Wang

et al.

Experimental Brain Research, Journal Year: 2023, Volume and Issue: 242(2), P. 375 - 384

Published: Dec. 21, 2023

Language: Английский

Citations

4

The relationship of bispectral index values to conscious state: an analysis of two volunteer cohort studies DOI
Jordan Wehrman, Peter J. Schuller, Cameron Casey

et al.

British Journal of Anaesthesia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

1

The Thalamus in Perioperative Neurocognitive Disorders DOI
Marinus Fislage, Norman Zacharias, Insa Feinkohl

et al.

Neuropsychology Review, Journal Year: 2023, Volume and Issue: 34(3), P. 850 - 859

Published: Sept. 22, 2023

Language: Английский

Citations

3