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    Pfizer Inc medetomidine
    Apparent Diffusion Coefficient (ADC) and Blood Oxygenation Level—Dependent (BOLD) changes and time courses for each dosage of both anesthetic conditions. Averaged ADCs of whole brains for each dosage of isoflurane (A; n = 10) and <t>medetomidine</t> (B; n = 8). Averaged BOLD signal change ratios of whole brain for each dosage of isoflurane (C; n = 6) and medetomidine (D; n = 7). Averaged time courses of ADCs (E, F) and BOLD signal changes ratios (G, H) at whole brains for each dosage of isoflurane (E, G) and medetomidine (F, H), showing the stability of the ADC change while the BOLD signal exhibits a significant negative drift with time. Note that the BOLD change levels for each medetomidine dosage are inverted between E and H. Mean arterial blood pressure (MABP) under each dosage of isoflurane (I; n = 5) and medetomidine (J; n = 5). Bar plots exhibit mean ± standard error of the mean (SEM). * p
    Medetomidine, supplied by Pfizer Inc, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/medetomidine/product/Pfizer Inc
    Average 86 stars, based on 1 article reviews
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    86
    Orion Corporation medetomidine
    Anaesthetic parameters of adult zebrafish when treated with different anaesthetic protocols. A) Equilibrium loss, B) anaesthesia induction, C) loss of reaction to a soft stimulus, D) loss of reaction to a painful stimulus, E) initiation of the movements, and F) equilibrium recovery of adult zebrafish after being subjected to an anaesthetic bath of: 100 μg/mL MS-222 (MS), 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL <t>medetomidine</t> (K+M); or 100 μg/mL ketamine + 1.25 μg/mL medetomidine / 3.125 μg/mL atipamezole (K+M/A). Each point represents an animal (n = 8). Data are expressed as median [interquartile range]. *p
    Medetomidine, supplied by Orion Corporation, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/medetomidine/product/Orion Corporation
    Average 86 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    medetomidine - by Bioz Stars, 2021-03
    86/100 stars
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    86
    Zenyaku Kogyo Co Ltd medetomidine
    Fitting of dark-adapted ERG b-waves. A : Representative b-wave fitting waveforms of midazolam, <t>medetomidine,</t> and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX). The log light intensity at half maximum amplitude ( K ), maximum amplitude ( R max ), log R max , and n parameters of each group are shown in B , C , and D , respectively. B : Note that the K of the mice administered pentobarbital sodium was larger than that of the mice administered MMB. Statistically significant differences are indicated by * for p
    Medetomidine, supplied by Zenyaku Kogyo Co Ltd, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/medetomidine/product/Zenyaku Kogyo Co Ltd
    Average 86 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    medetomidine - by Bioz Stars, 2021-03
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    86
    Zoetis medetomidine
    Anesthetic protocols and fMRI acquisition. (a) The general outline of the applied anesthetic protocols. For all four protocols (see Table 1 ), isoflurane was used to induce unconsciousness (5%) and during animal preparation (2-3%). For protocols 1, 2, and 4, a bolus of <t>medetomidine</t> was given after the preparation phase, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus. The bolus was omitted for protocol 3, with continuous infusion starting directly after preparation, and isoflurane being gradually reduced to zero over the course of 20 – 25 min. Anesthesia was maintained for a maximum of six hours since the start of medetomidine administration (time = 0). In the end, animals were provided with 2% isoflurane and freed from all equipment. Atipamezole was injected SC to antagonize medetomidine effects and to facilitate a smooth recovery. (b) Multiple fMRI runs were acquired per anesthesia session, with consecutive runs being alternated between somatosensory fMRI with electrical forepaw stimulation (EFS-fMRI) and resting state fMRI (RS-fMRI) with no stimulus. The stimulation paradigm applied during EFS-fMRI runs is shown in (c) .
    Medetomidine, supplied by Zoetis, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/medetomidine/product/Zoetis
    Average 86 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    medetomidine - by Bioz Stars, 2021-03
    86/100 stars
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    Image Search Results


    Apparent Diffusion Coefficient (ADC) and Blood Oxygenation Level—Dependent (BOLD) changes and time courses for each dosage of both anesthetic conditions. Averaged ADCs of whole brains for each dosage of isoflurane (A; n = 10) and medetomidine (B; n = 8). Averaged BOLD signal change ratios of whole brain for each dosage of isoflurane (C; n = 6) and medetomidine (D; n = 7). Averaged time courses of ADCs (E, F) and BOLD signal changes ratios (G, H) at whole brains for each dosage of isoflurane (E, G) and medetomidine (F, H), showing the stability of the ADC change while the BOLD signal exhibits a significant negative drift with time. Note that the BOLD change levels for each medetomidine dosage are inverted between E and H. Mean arterial blood pressure (MABP) under each dosage of isoflurane (I; n = 5) and medetomidine (J; n = 5). Bar plots exhibit mean ± standard error of the mean (SEM). * p

    Journal: PLoS Biology

    Article Title: Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

    doi: 10.1371/journal.pbio.2001494

    Figure Lengend Snippet: Apparent Diffusion Coefficient (ADC) and Blood Oxygenation Level—Dependent (BOLD) changes and time courses for each dosage of both anesthetic conditions. Averaged ADCs of whole brains for each dosage of isoflurane (A; n = 10) and medetomidine (B; n = 8). Averaged BOLD signal change ratios of whole brain for each dosage of isoflurane (C; n = 6) and medetomidine (D; n = 7). Averaged time courses of ADCs (E, F) and BOLD signal changes ratios (G, H) at whole brains for each dosage of isoflurane (E, G) and medetomidine (F, H), showing the stability of the ADC change while the BOLD signal exhibits a significant negative drift with time. Note that the BOLD change levels for each medetomidine dosage are inverted between E and H. Mean arterial blood pressure (MABP) under each dosage of isoflurane (I; n = 5) and medetomidine (J; n = 5). Bar plots exhibit mean ± standard error of the mean (SEM). * p

    Article Snippet: For the medetomidine group, the isoflurane anesthesia was discontinued while the animals received a subcutaneous bolus of 0.05 mg/kg medetomidine (Domitor; Pfizer Animal Health, New York, NY, USA) at the end of the animal preparation.

    Techniques: Diffusion-based Assay

    Comparison of Apparent Diffusion Coefficient (ADC) and Blood Oxygenation Level—Dependent (BOLD) changes with Local Field Potentials (LFPs) in the Central Medial (CM) and Ventral Posterolateral (VPL) thalamic nuclei. BOLD changes under each dosage of isoflurane (A) and medetomidine (B) at the CM and the VPL. Region of interest (ROI) locations for the CM and the VPL are overlaid on structural images. ADC changes under each dosage of isoflurane (C) and medetomidine (D) at the CM and the VPL. (E) Representative LFP signals in a single animal at the CM (upper) and the VPL (below), for each dosage of isoflurane and medetomidine. Total LFP power (frequency range: 1–70 Hz) under each dosage of isoflurane (F; n = 8 for CM, n = 8 for VPL) and medetomidine (G; n = 8 for CM, n = 8 for VPL). Bar plots exhibit mean ± the standard error of the mean (SEM). * p

    Journal: PLoS Biology

    Article Title: Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

    doi: 10.1371/journal.pbio.2001494

    Figure Lengend Snippet: Comparison of Apparent Diffusion Coefficient (ADC) and Blood Oxygenation Level—Dependent (BOLD) changes with Local Field Potentials (LFPs) in the Central Medial (CM) and Ventral Posterolateral (VPL) thalamic nuclei. BOLD changes under each dosage of isoflurane (A) and medetomidine (B) at the CM and the VPL. Region of interest (ROI) locations for the CM and the VPL are overlaid on structural images. ADC changes under each dosage of isoflurane (C) and medetomidine (D) at the CM and the VPL. (E) Representative LFP signals in a single animal at the CM (upper) and the VPL (below), for each dosage of isoflurane and medetomidine. Total LFP power (frequency range: 1–70 Hz) under each dosage of isoflurane (F; n = 8 for CM, n = 8 for VPL) and medetomidine (G; n = 8 for CM, n = 8 for VPL). Bar plots exhibit mean ± the standard error of the mean (SEM). * p

    Article Snippet: For the medetomidine group, the isoflurane anesthesia was discontinued while the animals received a subcutaneous bolus of 0.05 mg/kg medetomidine (Domitor; Pfizer Animal Health, New York, NY, USA) at the end of the animal preparation.

    Techniques: Diffusion-based Assay

    Comparison of Blood Oxygenation Level—Dependent (BOLD) and Apparent Diffusion Coefficient (ADC) maps under both anesthetic conditions. (A, B) T-maps of changes in BOLD signals (A 1 ; n = 6, A 2 ; n = 7) and ADC (B 1 ; n = 10, B 2 ; n = 8) under isoflurane (iso) and medetomidine (med) dosage conditions (six out of ten slices are shown. Hot colors mean an increase in BOLD or ADC of high dose (cluster-level corrected p

    Journal: PLoS Biology

    Article Title: Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

    doi: 10.1371/journal.pbio.2001494

    Figure Lengend Snippet: Comparison of Blood Oxygenation Level—Dependent (BOLD) and Apparent Diffusion Coefficient (ADC) maps under both anesthetic conditions. (A, B) T-maps of changes in BOLD signals (A 1 ; n = 6, A 2 ; n = 7) and ADC (B 1 ; n = 10, B 2 ; n = 8) under isoflurane (iso) and medetomidine (med) dosage conditions (six out of ten slices are shown. Hot colors mean an increase in BOLD or ADC of high dose (cluster-level corrected p

    Article Snippet: For the medetomidine group, the isoflurane anesthesia was discontinued while the animals received a subcutaneous bolus of 0.05 mg/kg medetomidine (Domitor; Pfizer Animal Health, New York, NY, USA) at the end of the animal preparation.

    Techniques: Diffusion-based Assay

    Effects of furosemide infusion in the Central Medial thalamus nucleus (CM) on the Apparent Diffusion Coefficient (ADC), Local Field Potentials (LFPs) and awake response threshold under 0.1 mg/kg/h medetomidine condition. (A) Percentage of animals exhibiting an awake response during CM electrical stimulation after the CM infusion with furosemide (Furo; n = 6). (B) Average ADC change in the CM and cingulate cortex (Cg) before and after CM infusion ( n = 6 for artificial cerebrospinal fluid [aCSF], n = 6 for Furosemide). Average time course of ADC change in the CM (C) and Cg (D) with the infusion of aCSF and furosemide. (E) Representative local field potentials (LFP) signals at the CM and Cg with the CM infusion with aCSF (upper) or furosemide (below). (F) Total LFP power (frequency range: 1–70 Hz) in the CM and Cg, before and after CM infusion with furosemide ( n = 6) or aCSF ( n = 6). Time course and bar plots exhibit mean ± the standard error of the mean (SEM). ** p

    Journal: PLoS Biology

    Article Title: Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

    doi: 10.1371/journal.pbio.2001494

    Figure Lengend Snippet: Effects of furosemide infusion in the Central Medial thalamus nucleus (CM) on the Apparent Diffusion Coefficient (ADC), Local Field Potentials (LFPs) and awake response threshold under 0.1 mg/kg/h medetomidine condition. (A) Percentage of animals exhibiting an awake response during CM electrical stimulation after the CM infusion with furosemide (Furo; n = 6). (B) Average ADC change in the CM and cingulate cortex (Cg) before and after CM infusion ( n = 6 for artificial cerebrospinal fluid [aCSF], n = 6 for Furosemide). Average time course of ADC change in the CM (C) and Cg (D) with the infusion of aCSF and furosemide. (E) Representative local field potentials (LFP) signals at the CM and Cg with the CM infusion with aCSF (upper) or furosemide (below). (F) Total LFP power (frequency range: 1–70 Hz) in the CM and Cg, before and after CM infusion with furosemide ( n = 6) or aCSF ( n = 6). Time course and bar plots exhibit mean ± the standard error of the mean (SEM). ** p

    Article Snippet: For the medetomidine group, the isoflurane anesthesia was discontinued while the animals received a subcutaneous bolus of 0.05 mg/kg medetomidine (Domitor; Pfizer Animal Health, New York, NY, USA) at the end of the animal preparation.

    Techniques: Diffusion-based Assay

    Summarized relationship of the Apparent Diffusion Coefficient (ADC) with underlying neural activity status in the Central Medial thalamic nucleus (CM). Scatter plots between local field potential (LFP) power and ADC (A) or blood oxygenation level—dependent (BOLD) change ratio (B) in the CM under all anesthetic conditions (isoflurane: 1.5%, 2.0%, and 2.5%; medetomidine: 0.1 and 0.3 mg/kg/h). Scatter plots of CM ADC (C) and CM BOLD change ratio (D) with the threshold amplitude to trigger an awake response during CM electrical stimulation under anesthesia with 0.1 and 0.3 mg/kg/h of medetomidine. (E) Scatter plots between CM ADC and the threshold amplitude to trigger an awake response under anesthesia (0.1 mg/kg/h medetomidine) before and after CM infusion of furosemide and H-80. Data with anesthetic dosages for the CM of individual rats can be found in S1 Data for ADC and S2 Data for BOLD. LFP power data with anesthetic dosages for CM of individual rats can be found in S4 Data . Data for minimum amplitudes of individual rats can be found in S5 Data . ADC data for pharmacological diffusion functional MRI (DfMRI) of individual rats found in S3 Data .

    Journal: PLoS Biology

    Article Title: Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

    doi: 10.1371/journal.pbio.2001494

    Figure Lengend Snippet: Summarized relationship of the Apparent Diffusion Coefficient (ADC) with underlying neural activity status in the Central Medial thalamic nucleus (CM). Scatter plots between local field potential (LFP) power and ADC (A) or blood oxygenation level—dependent (BOLD) change ratio (B) in the CM under all anesthetic conditions (isoflurane: 1.5%, 2.0%, and 2.5%; medetomidine: 0.1 and 0.3 mg/kg/h). Scatter plots of CM ADC (C) and CM BOLD change ratio (D) with the threshold amplitude to trigger an awake response during CM electrical stimulation under anesthesia with 0.1 and 0.3 mg/kg/h of medetomidine. (E) Scatter plots between CM ADC and the threshold amplitude to trigger an awake response under anesthesia (0.1 mg/kg/h medetomidine) before and after CM infusion of furosemide and H-80. Data with anesthetic dosages for the CM of individual rats can be found in S1 Data for ADC and S2 Data for BOLD. LFP power data with anesthetic dosages for CM of individual rats can be found in S4 Data . Data for minimum amplitudes of individual rats can be found in S5 Data . ADC data for pharmacological diffusion functional MRI (DfMRI) of individual rats found in S3 Data .

    Article Snippet: For the medetomidine group, the isoflurane anesthesia was discontinued while the animals received a subcutaneous bolus of 0.05 mg/kg medetomidine (Domitor; Pfizer Animal Health, New York, NY, USA) at the end of the animal preparation.

    Techniques: Diffusion-based Assay, Activity Assay, Functional Assay, Magnetic Resonance Imaging

    Effects of electrical stimulation of the Central Medial thalamus nucleus (CM) on anesthetic status. (A) Percentage of animals exhibiting an awake response during the electrical stimulation at the CM and VPL under 0.1 mg/kg/h medetomidine condition ( n = 6). (B) Representative electromyography (EMG) signals of the stimulation, with 0.8 mA amplitude at the CM and the VPL under 0.1 mg/kg/h medetomidine. (C) Percentage of animals exhibiting an awake response during the electrical stimulation at the CM, with an amplitude of 0.3–1.2 mA under 0.1 and 0.3 mg/kg/h medetomidine ( n = 6). (D) Percentage of animals exhibiting an awake response during the electrical stimulation at the six brain locations under 0.1 mg/kg/h medetomidine ( n = 4). # p

    Journal: PLoS Biology

    Article Title: Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

    doi: 10.1371/journal.pbio.2001494

    Figure Lengend Snippet: Effects of electrical stimulation of the Central Medial thalamus nucleus (CM) on anesthetic status. (A) Percentage of animals exhibiting an awake response during the electrical stimulation at the CM and VPL under 0.1 mg/kg/h medetomidine condition ( n = 6). (B) Representative electromyography (EMG) signals of the stimulation, with 0.8 mA amplitude at the CM and the VPL under 0.1 mg/kg/h medetomidine. (C) Percentage of animals exhibiting an awake response during the electrical stimulation at the CM, with an amplitude of 0.3–1.2 mA under 0.1 and 0.3 mg/kg/h medetomidine ( n = 6). (D) Percentage of animals exhibiting an awake response during the electrical stimulation at the six brain locations under 0.1 mg/kg/h medetomidine ( n = 4). # p

    Article Snippet: For the medetomidine group, the isoflurane anesthesia was discontinued while the animals received a subcutaneous bolus of 0.05 mg/kg medetomidine (Domitor; Pfizer Animal Health, New York, NY, USA) at the end of the animal preparation.

    Techniques:

    Anaesthetic parameters of adult zebrafish when treated with different anaesthetic protocols. A) Equilibrium loss, B) anaesthesia induction, C) loss of reaction to a soft stimulus, D) loss of reaction to a painful stimulus, E) initiation of the movements, and F) equilibrium recovery of adult zebrafish after being subjected to an anaesthetic bath of: 100 μg/mL MS-222 (MS), 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL medetomidine (K+M); or 100 μg/mL ketamine + 1.25 μg/mL medetomidine / 3.125 μg/mL atipamezole (K+M/A). Each point represents an animal (n = 8). Data are expressed as median [interquartile range]. *p

    Journal: PLoS ONE

    Article Title: Evaluation of anaesthetic protocols for laboratory adult zebrafish (Danio rerio)

    doi: 10.1371/journal.pone.0197846

    Figure Lengend Snippet: Anaesthetic parameters of adult zebrafish when treated with different anaesthetic protocols. A) Equilibrium loss, B) anaesthesia induction, C) loss of reaction to a soft stimulus, D) loss of reaction to a painful stimulus, E) initiation of the movements, and F) equilibrium recovery of adult zebrafish after being subjected to an anaesthetic bath of: 100 μg/mL MS-222 (MS), 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL medetomidine (K+M); or 100 μg/mL ketamine + 1.25 μg/mL medetomidine / 3.125 μg/mL atipamezole (K+M/A). Each point represents an animal (n = 8). Data are expressed as median [interquartile range]. *p

    Article Snippet: The following drugs were used in the present study: Etomidate (2 mg/mL, Lipuro, B. Braun, Melsungen, Germany); Propofol (10 mg/mL, Lipuro, Braun VetCare SA, Barcelona, Spain); Lidocaine (20 mg/mL, B.Braun Medical, Queluz de Baixo, Barcarena, Portugal); Ketamine (1 g/mL, Clorketam 1000, Vetoquinol S.A., Lure, France); Medetomidine (1 mg/mL, Domtor, Orion Corporation Orioninte, Espoo, Finland); Atipamezole (5 mg/mL, Antisedan, Orion Corporation Orioninte, Espoo, Finland).

    Techniques: Mass Spectrometry

    Respiratory rate (RR) per minute of adult zebrafish when treated with different anaesthetic protocols. A) RR after loss of equilibrium and B) RR after loss of soft stimulus response of adult zebrafish after being subjected to an anaesthetic bath of: 100 μg/mL MS-222 (MS), 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL medetomidine (K+M); or 100 μg/mL ketamine + 1.25 μg/mL medetomidine / 3.125 μg/mL atipamezole (K+M/A). Each point represents an animal (n = 8). Data are expressed as median [interquartile range]. *p

    Journal: PLoS ONE

    Article Title: Evaluation of anaesthetic protocols for laboratory adult zebrafish (Danio rerio)

    doi: 10.1371/journal.pone.0197846

    Figure Lengend Snippet: Respiratory rate (RR) per minute of adult zebrafish when treated with different anaesthetic protocols. A) RR after loss of equilibrium and B) RR after loss of soft stimulus response of adult zebrafish after being subjected to an anaesthetic bath of: 100 μg/mL MS-222 (MS), 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL medetomidine (K+M); or 100 μg/mL ketamine + 1.25 μg/mL medetomidine / 3.125 μg/mL atipamezole (K+M/A). Each point represents an animal (n = 8). Data are expressed as median [interquartile range]. *p

    Article Snippet: The following drugs were used in the present study: Etomidate (2 mg/mL, Lipuro, B. Braun, Melsungen, Germany); Propofol (10 mg/mL, Lipuro, Braun VetCare SA, Barcelona, Spain); Lidocaine (20 mg/mL, B.Braun Medical, Queluz de Baixo, Barcarena, Portugal); Ketamine (1 g/mL, Clorketam 1000, Vetoquinol S.A., Lure, France); Medetomidine (1 mg/mL, Domtor, Orion Corporation Orioninte, Espoo, Finland); Atipamezole (5 mg/mL, Antisedan, Orion Corporation Orioninte, Espoo, Finland).

    Techniques: Mass Spectrometry

    Number of crossings per minute of adult zebrafish through the longitudinal line of the tank after being treated with different anaesthetic protocols. The activity of zebrafish was analysed at A) 5 h and B) 24 h after being subjected to the following anaesthetic baths: 100 μg/mL MS-222 (MS), 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL medetomidine (K+M); or 100 μg/mL ketamine + 1.25 μg/mL medetomidine / 3.125 μg/mL atipamezole (K+M/A). A group of non-anaesthetized animals served as Control. Each point represents an animal (n = 4 for control group; n = 8 for all other groups). Data are expressed as median [interquartile range]. *p

    Journal: PLoS ONE

    Article Title: Evaluation of anaesthetic protocols for laboratory adult zebrafish (Danio rerio)

    doi: 10.1371/journal.pone.0197846

    Figure Lengend Snippet: Number of crossings per minute of adult zebrafish through the longitudinal line of the tank after being treated with different anaesthetic protocols. The activity of zebrafish was analysed at A) 5 h and B) 24 h after being subjected to the following anaesthetic baths: 100 μg/mL MS-222 (MS), 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL medetomidine (K+M); or 100 μg/mL ketamine + 1.25 μg/mL medetomidine / 3.125 μg/mL atipamezole (K+M/A). A group of non-anaesthetized animals served as Control. Each point represents an animal (n = 4 for control group; n = 8 for all other groups). Data are expressed as median [interquartile range]. *p

    Article Snippet: The following drugs were used in the present study: Etomidate (2 mg/mL, Lipuro, B. Braun, Melsungen, Germany); Propofol (10 mg/mL, Lipuro, Braun VetCare SA, Barcelona, Spain); Lidocaine (20 mg/mL, B.Braun Medical, Queluz de Baixo, Barcarena, Portugal); Ketamine (1 g/mL, Clorketam 1000, Vetoquinol S.A., Lure, France); Medetomidine (1 mg/mL, Domtor, Orion Corporation Orioninte, Espoo, Finland); Atipamezole (5 mg/mL, Antisedan, Orion Corporation Orioninte, Espoo, Finland).

    Techniques: Activity Assay, Mass Spectrometry

    Fitting of dark-adapted ERG b-waves. A : Representative b-wave fitting waveforms of midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX). The log light intensity at half maximum amplitude ( K ), maximum amplitude ( R max ), log R max , and n parameters of each group are shown in B , C , and D , respectively. B : Note that the K of the mice administered pentobarbital sodium was larger than that of the mice administered MMB. Statistically significant differences are indicated by * for p

    Journal: Molecular Vision

    Article Title: Effect of midazolam, medetomidine, and butorphanol tartrate combination anesthetic on electroretinograms of mice

    doi:

    Figure Lengend Snippet: Fitting of dark-adapted ERG b-waves. A : Representative b-wave fitting waveforms of midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX). The log light intensity at half maximum amplitude ( K ), maximum amplitude ( R max ), log R max , and n parameters of each group are shown in B , C , and D , respectively. B : Note that the K of the mice administered pentobarbital sodium was larger than that of the mice administered MMB. Statistically significant differences are indicated by * for p

    Article Snippet: Drugs The MMB combination anesthetic contained midazolam (4 mg/kg, SANDOZ, Yamagata, Japan), medetomidine (0.75 mg/kg, Nippon Zenyaku Kogyo Co., Ltd, Fukushima, Japan), and butorphanol tartrate (5 mg/kg, Meiji Seika Pharma, Tokyo, Japan).

    Techniques: Mouse Assay

    Fitting of dark-adapted ERG a-waves. A : Representative a-wave fitting waveforms of midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX). The log sensitivity ( S ), log maximum amplitude ( R max ), and delay before the onset of the a-wave ( T d ) parameters of each group are shown in B , C , and D , respectively. D : Note that the T d of the mice administered MMB and pentobarbital sodium was larger than that of the mice administered KX. Statistically significant differences are indicated by ** for p

    Journal: Molecular Vision

    Article Title: Effect of midazolam, medetomidine, and butorphanol tartrate combination anesthetic on electroretinograms of mice

    doi:

    Figure Lengend Snippet: Fitting of dark-adapted ERG a-waves. A : Representative a-wave fitting waveforms of midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX). The log sensitivity ( S ), log maximum amplitude ( R max ), and delay before the onset of the a-wave ( T d ) parameters of each group are shown in B , C , and D , respectively. D : Note that the T d of the mice administered MMB and pentobarbital sodium was larger than that of the mice administered KX. Statistically significant differences are indicated by ** for p

    Article Snippet: Drugs The MMB combination anesthetic contained midazolam (4 mg/kg, SANDOZ, Yamagata, Japan), medetomidine (0.75 mg/kg, Nippon Zenyaku Kogyo Co., Ltd, Fukushima, Japan), and butorphanol tartrate (5 mg/kg, Meiji Seika Pharma, Tokyo, Japan).

    Techniques: Mouse Assay

    Light-adapted ERGs. A : Representative light-adapted electroretinogram (ERG) recordings performed with midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX) against a white background. B : The waveforms processed with a 30 Hz low-pass filter for b-wave fitting.

    Journal: Molecular Vision

    Article Title: Effect of midazolam, medetomidine, and butorphanol tartrate combination anesthetic on electroretinograms of mice

    doi:

    Figure Lengend Snippet: Light-adapted ERGs. A : Representative light-adapted electroretinogram (ERG) recordings performed with midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX) against a white background. B : The waveforms processed with a 30 Hz low-pass filter for b-wave fitting.

    Article Snippet: Drugs The MMB combination anesthetic contained midazolam (4 mg/kg, SANDOZ, Yamagata, Japan), medetomidine (0.75 mg/kg, Nippon Zenyaku Kogyo Co., Ltd, Fukushima, Japan), and butorphanol tartrate (5 mg/kg, Meiji Seika Pharma, Tokyo, Japan).

    Techniques:

    Dark-adapted ERGs representing scotopic OPs. Oscillatory potentials (OPs) were recorded under dark adaptation in response to a flash at intensity of 50 cd.s/m 2 . A : Representative waveforms of electroretinogram (ERG) performed with midazolam, medetomidine, and butorphanol tartrate (MMB (left), pentobarbital sodium (PS; center), and ketamine/xylazine (KX; right). The waveforms were processed with a 65 Hz high-pass filter and a 300 Hz low-pass filter to quantify the OPs. B : The amplitude of the OPs. Note that the amplitude of the OPs in the mice administered MMB was statistically significantly larger than that in the mice administered pentobarbital sodium except OP1 and OP2. The amplitude of the OPs in the mice administered MMB was statistically significantly larger than that in the mice administered KX for OP3. The amplitude of the OPs in the mice administered KX tended to be larger than the amplitude of the mice administered PS. C : Note that the implicit time of the OPs in the mice administered PS was statistically significantly delayed compared to the mice administered KX except OP1. The implicit time of the OPs in the mice administered PS showed a tendency for delay compared to the mice administered MMB. Statistically significant differences are indicated as *p

    Journal: Molecular Vision

    Article Title: Effect of midazolam, medetomidine, and butorphanol tartrate combination anesthetic on electroretinograms of mice

    doi:

    Figure Lengend Snippet: Dark-adapted ERGs representing scotopic OPs. Oscillatory potentials (OPs) were recorded under dark adaptation in response to a flash at intensity of 50 cd.s/m 2 . A : Representative waveforms of electroretinogram (ERG) performed with midazolam, medetomidine, and butorphanol tartrate (MMB (left), pentobarbital sodium (PS; center), and ketamine/xylazine (KX; right). The waveforms were processed with a 65 Hz high-pass filter and a 300 Hz low-pass filter to quantify the OPs. B : The amplitude of the OPs. Note that the amplitude of the OPs in the mice administered MMB was statistically significantly larger than that in the mice administered pentobarbital sodium except OP1 and OP2. The amplitude of the OPs in the mice administered MMB was statistically significantly larger than that in the mice administered KX for OP3. The amplitude of the OPs in the mice administered KX tended to be larger than the amplitude of the mice administered PS. C : Note that the implicit time of the OPs in the mice administered PS was statistically significantly delayed compared to the mice administered KX except OP1. The implicit time of the OPs in the mice administered PS showed a tendency for delay compared to the mice administered MMB. Statistically significant differences are indicated as *p

    Article Snippet: Drugs The MMB combination anesthetic contained midazolam (4 mg/kg, SANDOZ, Yamagata, Japan), medetomidine (0.75 mg/kg, Nippon Zenyaku Kogyo Co., Ltd, Fukushima, Japan), and butorphanol tartrate (5 mg/kg, Meiji Seika Pharma, Tokyo, Japan).

    Techniques: Mouse Assay

    Fitting of light-adapted ERG b-waves. A : Representative light-adapted b-wave fitting waveforms of midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX). Log light intensity at half maximum amplitude ( K ), log maximum amplitude ( R max ), and n parameters of each group are shown in B , C , and D , respectively. Note that there were no statistically significant differences between the three groups.

    Journal: Molecular Vision

    Article Title: Effect of midazolam, medetomidine, and butorphanol tartrate combination anesthetic on electroretinograms of mice

    doi:

    Figure Lengend Snippet: Fitting of light-adapted ERG b-waves. A : Representative light-adapted b-wave fitting waveforms of midazolam, medetomidine, and butorphanol tartrate (MMB), pentobarbital sodium, and ketamine/xylazine (KX). Log light intensity at half maximum amplitude ( K ), log maximum amplitude ( R max ), and n parameters of each group are shown in B , C , and D , respectively. Note that there were no statistically significant differences between the three groups.

    Article Snippet: Drugs The MMB combination anesthetic contained midazolam (4 mg/kg, SANDOZ, Yamagata, Japan), medetomidine (0.75 mg/kg, Nippon Zenyaku Kogyo Co., Ltd, Fukushima, Japan), and butorphanol tartrate (5 mg/kg, Meiji Seika Pharma, Tokyo, Japan).

    Techniques:

    Dark-adapted ERGs. A : Representative electroretinogram (ERG) recordings performed with midazolam, medetomidine, and butorphanol tartrate (MMB; left), pentobarbital sodium (center), and ketamine/xylazine (KX; right). B : The waveforms processed with a 30 Hz low-pass filter for b-wave fitting.

    Journal: Molecular Vision

    Article Title: Effect of midazolam, medetomidine, and butorphanol tartrate combination anesthetic on electroretinograms of mice

    doi:

    Figure Lengend Snippet: Dark-adapted ERGs. A : Representative electroretinogram (ERG) recordings performed with midazolam, medetomidine, and butorphanol tartrate (MMB; left), pentobarbital sodium (center), and ketamine/xylazine (KX; right). B : The waveforms processed with a 30 Hz low-pass filter for b-wave fitting.

    Article Snippet: Drugs The MMB combination anesthetic contained midazolam (4 mg/kg, SANDOZ, Yamagata, Japan), medetomidine (0.75 mg/kg, Nippon Zenyaku Kogyo Co., Ltd, Fukushima, Japan), and butorphanol tartrate (5 mg/kg, Meiji Seika Pharma, Tokyo, Japan).

    Techniques:

    Anesthetic protocols and fMRI acquisition. (a) The general outline of the applied anesthetic protocols. For all four protocols (see Table 1 ), isoflurane was used to induce unconsciousness (5%) and during animal preparation (2-3%). For protocols 1, 2, and 4, a bolus of medetomidine was given after the preparation phase, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus. The bolus was omitted for protocol 3, with continuous infusion starting directly after preparation, and isoflurane being gradually reduced to zero over the course of 20 – 25 min. Anesthesia was maintained for a maximum of six hours since the start of medetomidine administration (time = 0). In the end, animals were provided with 2% isoflurane and freed from all equipment. Atipamezole was injected SC to antagonize medetomidine effects and to facilitate a smooth recovery. (b) Multiple fMRI runs were acquired per anesthesia session, with consecutive runs being alternated between somatosensory fMRI with electrical forepaw stimulation (EFS-fMRI) and resting state fMRI (RS-fMRI) with no stimulus. The stimulation paradigm applied during EFS-fMRI runs is shown in (c) .

    Journal: bioRxiv

    Article Title: Temporal stability of fMRI in medetomidine-anesthetized rats

    doi: 10.1101/667659

    Figure Lengend Snippet: Anesthetic protocols and fMRI acquisition. (a) The general outline of the applied anesthetic protocols. For all four protocols (see Table 1 ), isoflurane was used to induce unconsciousness (5%) and during animal preparation (2-3%). For protocols 1, 2, and 4, a bolus of medetomidine was given after the preparation phase, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus. The bolus was omitted for protocol 3, with continuous infusion starting directly after preparation, and isoflurane being gradually reduced to zero over the course of 20 – 25 min. Anesthesia was maintained for a maximum of six hours since the start of medetomidine administration (time = 0). In the end, animals were provided with 2% isoflurane and freed from all equipment. Atipamezole was injected SC to antagonize medetomidine effects and to facilitate a smooth recovery. (b) Multiple fMRI runs were acquired per anesthesia session, with consecutive runs being alternated between somatosensory fMRI with electrical forepaw stimulation (EFS-fMRI) and resting state fMRI (RS-fMRI) with no stimulus. The stimulation paradigm applied during EFS-fMRI runs is shown in (c) .

    Article Snippet: For protocols 1, 2, and 4, medetomidine (Dorbene vet, Zoetis Deutschland GmbH, Germany) was initially given as a bolus loading dose, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus.

    Techniques: Injection

    Areas activated by electrical forepaw stimulation (EFS). (a) An activation probability map produced by pooling significantly active clusters across all 283 EFS-fMRI runs (left). On the right, the EFS-fMRI runs are grouped according to the applied medetomidine protocol and to the time since the start of medetomidine administration (early: 0 – 2 h; middle: 2 – 4 h; late: 4 – 6 h), to produce separate activation probability maps for each group. All maps are thresholded at 3% and overlaid on a T2-weighted structural study template. The asterisk marks the crossing of the anterior commissure (AC, −0.36 mm relative to the bregma, according to the Paxinos-Watson rat brain atlas). The rest of the slices shown on the left are taken at 1 mm intervals from the AC slice. On the right, only the slice containing the peak activation, 2 mm rostral to AC, is shown for each group. (b) The only consistently active cluster across all runs corresponds to the forelimb region of the left primary somatosensory cortex (S1FL). The location of this cluster is shown alongside the anatomical delineation of the same area from the Paxinos-Watson rat brain atlas. The functionally defined S1FL (area active in > 30% of all EFS-fMRI runs) is set as a region-of-interest (ROI) for the extraction of BOLD signal time courses. Such a time course is shown for one example EFS-fMRI run, with the stimulation blocks marked by horizontal lines. Averaging the three stimulation blocks results in an event-related average, from which the peak % signal change (peak ΔBOLD) can be extracted. Event-related average responses (mean ± s.d.) are plotted for all four medetomidine protocols (c) and compared to the model response (d) . The model is generated by convolving the stimulus paradigm (1 during EFS, 0 otherwise) with a double-gamma hemodynamic response function (using the default parameters of FEAT version 6.00, part of FSL); it is shown here rescaled to the y-axis range of the event-related averages, to aid visual comparison.

    Journal: bioRxiv

    Article Title: Temporal stability of fMRI in medetomidine-anesthetized rats

    doi: 10.1101/667659

    Figure Lengend Snippet: Areas activated by electrical forepaw stimulation (EFS). (a) An activation probability map produced by pooling significantly active clusters across all 283 EFS-fMRI runs (left). On the right, the EFS-fMRI runs are grouped according to the applied medetomidine protocol and to the time since the start of medetomidine administration (early: 0 – 2 h; middle: 2 – 4 h; late: 4 – 6 h), to produce separate activation probability maps for each group. All maps are thresholded at 3% and overlaid on a T2-weighted structural study template. The asterisk marks the crossing of the anterior commissure (AC, −0.36 mm relative to the bregma, according to the Paxinos-Watson rat brain atlas). The rest of the slices shown on the left are taken at 1 mm intervals from the AC slice. On the right, only the slice containing the peak activation, 2 mm rostral to AC, is shown for each group. (b) The only consistently active cluster across all runs corresponds to the forelimb region of the left primary somatosensory cortex (S1FL). The location of this cluster is shown alongside the anatomical delineation of the same area from the Paxinos-Watson rat brain atlas. The functionally defined S1FL (area active in > 30% of all EFS-fMRI runs) is set as a region-of-interest (ROI) for the extraction of BOLD signal time courses. Such a time course is shown for one example EFS-fMRI run, with the stimulation blocks marked by horizontal lines. Averaging the three stimulation blocks results in an event-related average, from which the peak % signal change (peak ΔBOLD) can be extracted. Event-related average responses (mean ± s.d.) are plotted for all four medetomidine protocols (c) and compared to the model response (d) . The model is generated by convolving the stimulus paradigm (1 during EFS, 0 otherwise) with a double-gamma hemodynamic response function (using the default parameters of FEAT version 6.00, part of FSL); it is shown here rescaled to the y-axis range of the event-related averages, to aid visual comparison.

    Article Snippet: For protocols 1, 2, and 4, medetomidine (Dorbene vet, Zoetis Deutschland GmbH, Germany) was initially given as a bolus loading dose, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus.

    Techniques: Activation Assay, Produced, Generated

    Anesthesia duration and physiology. (a) Anesthesia duration is plotted (dots) separately for bench and fMRI sessions, across all four medetomidine protocols. The bars represent a histogram of anesthesia durations, with all 48 anesthesia sessions binned into one-hour intervals. (b) Heart and respiratory rates (in beats/breaths per minute—bpm), pooled from both bench and fMRI sessions of each medetomidine protocol, are plotted as an across-session mean (solid line) ± s.d. (shaded area).

    Journal: bioRxiv

    Article Title: Temporal stability of fMRI in medetomidine-anesthetized rats

    doi: 10.1101/667659

    Figure Lengend Snippet: Anesthesia duration and physiology. (a) Anesthesia duration is plotted (dots) separately for bench and fMRI sessions, across all four medetomidine protocols. The bars represent a histogram of anesthesia durations, with all 48 anesthesia sessions binned into one-hour intervals. (b) Heart and respiratory rates (in beats/breaths per minute—bpm), pooled from both bench and fMRI sessions of each medetomidine protocol, are plotted as an across-session mean (solid line) ± s.d. (shaded area).

    Article Snippet: For protocols 1, 2, and 4, medetomidine (Dorbene vet, Zoetis Deutschland GmbH, Germany) was initially given as a bolus loading dose, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus.

    Techniques:

    Resting state functional connectivity (RSFC). (a) To calculate pair-wise RSFC, 28 regions-of-interest (ROIs) were defined based on the Paxinos-Watson rat brain atlas—14 on each hemisphere. Pearson’s correlations were calculated between the BOLD time courses of all unique ROI pairs and transformed into Fisher’s Z-scores. A pair-wise correlation matrix is shown for one example RS-fMRI run; the mean correlation (Z-score) across all ROI pairs constitutes the global RSFC. The matrix is also represented as a weighted network graph, with the ROIs as nodes and their pairs as edges. For visualization clarity, only the strongest 30% of edges are shown; edge thickness and opacity scale linearly with the relative rank of the correlation value (the highest Z-score corresponds to the thickest edge); node radius scales with the weighted degree (weighted sum of edges passing through the node). (b) The 295 RS-fMRI runs are split into 12 groups according to the applied medetomidine protocol and the time since the start of medetomidine administration (early: 0 – 2 h; middle: 2 – 4 h; late: 4 – 6 h). For each group, the upper triangular matrix represents the mean (across runs) pair-wise correlation, while the lower triangular matrix shows the change in correlation compared to each protocol’s early period. (c) The mean correlation matrices (upper triangles) are also visualized as network graphs, similarly to the example graph above. (d) Global RSFC values (dots) are plotted against the time of the RS-fMRI run acquisition. Solid lines correspond to the fit of a Linear Mixed Effects model (equation shown), with global RSFC as a response variable, time as a fixed effect, and individual rat intercepts as random effects; shaded areas represent the 95% confidence intervals of the fit. To test for time dependence, the constructed model was compared to a corresponding model lacking the time effect, using a Likelihood Ratio Test; the resulting p-values are shown.

    Journal: bioRxiv

    Article Title: Temporal stability of fMRI in medetomidine-anesthetized rats

    doi: 10.1101/667659

    Figure Lengend Snippet: Resting state functional connectivity (RSFC). (a) To calculate pair-wise RSFC, 28 regions-of-interest (ROIs) were defined based on the Paxinos-Watson rat brain atlas—14 on each hemisphere. Pearson’s correlations were calculated between the BOLD time courses of all unique ROI pairs and transformed into Fisher’s Z-scores. A pair-wise correlation matrix is shown for one example RS-fMRI run; the mean correlation (Z-score) across all ROI pairs constitutes the global RSFC. The matrix is also represented as a weighted network graph, with the ROIs as nodes and their pairs as edges. For visualization clarity, only the strongest 30% of edges are shown; edge thickness and opacity scale linearly with the relative rank of the correlation value (the highest Z-score corresponds to the thickest edge); node radius scales with the weighted degree (weighted sum of edges passing through the node). (b) The 295 RS-fMRI runs are split into 12 groups according to the applied medetomidine protocol and the time since the start of medetomidine administration (early: 0 – 2 h; middle: 2 – 4 h; late: 4 – 6 h). For each group, the upper triangular matrix represents the mean (across runs) pair-wise correlation, while the lower triangular matrix shows the change in correlation compared to each protocol’s early period. (c) The mean correlation matrices (upper triangles) are also visualized as network graphs, similarly to the example graph above. (d) Global RSFC values (dots) are plotted against the time of the RS-fMRI run acquisition. Solid lines correspond to the fit of a Linear Mixed Effects model (equation shown), with global RSFC as a response variable, time as a fixed effect, and individual rat intercepts as random effects; shaded areas represent the 95% confidence intervals of the fit. To test for time dependence, the constructed model was compared to a corresponding model lacking the time effect, using a Likelihood Ratio Test; the resulting p-values are shown.

    Article Snippet: For protocols 1, 2, and 4, medetomidine (Dorbene vet, Zoetis Deutschland GmbH, Germany) was initially given as a bolus loading dose, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus.

    Techniques: Functional Assay, Transformation Assay, Construct

    Temporal stability of stimulus-evoked responses. (a) Event-related averages produced by averaging the three electrical forepaw stimulation (EFS) blocks of each fMRI run. Single run traces are grouped according to the applied medetomidine protocol and the time since the start of medetomidine administration (early: 0 – 2 h; middle: 2 – 4 h; late: 4 – 6 h); each group’s mean event-related average is plotted as a thicker trace; EFS duration is represented by horizontal lines. The peak stimulus-evoked signal change (peak ΔBOLD) is extracted from the event-related averages and plotted in (c) ; dots represent single run values, while bars show the group mean. The same single-run peak ΔBOLD values are plotted in (b) against the exact time of data acquisition. Solid lines correspond to the fit of a Linear Mixed Effects model (equation shown), with peak ΔBOLD as a response variable, time as a fixed effect, and individual rat intercepts as random effects; shaded areas represent the 95% confidence intervals of the fit. To test for time dependence, the constructed models were compared to corresponding models lacking the time effect, using a Likelihood Ratio Test; the resulting p-values are shown.

    Journal: bioRxiv

    Article Title: Temporal stability of fMRI in medetomidine-anesthetized rats

    doi: 10.1101/667659

    Figure Lengend Snippet: Temporal stability of stimulus-evoked responses. (a) Event-related averages produced by averaging the three electrical forepaw stimulation (EFS) blocks of each fMRI run. Single run traces are grouped according to the applied medetomidine protocol and the time since the start of medetomidine administration (early: 0 – 2 h; middle: 2 – 4 h; late: 4 – 6 h); each group’s mean event-related average is plotted as a thicker trace; EFS duration is represented by horizontal lines. The peak stimulus-evoked signal change (peak ΔBOLD) is extracted from the event-related averages and plotted in (c) ; dots represent single run values, while bars show the group mean. The same single-run peak ΔBOLD values are plotted in (b) against the exact time of data acquisition. Solid lines correspond to the fit of a Linear Mixed Effects model (equation shown), with peak ΔBOLD as a response variable, time as a fixed effect, and individual rat intercepts as random effects; shaded areas represent the 95% confidence intervals of the fit. To test for time dependence, the constructed models were compared to corresponding models lacking the time effect, using a Likelihood Ratio Test; the resulting p-values are shown.

    Article Snippet: For protocols 1, 2, and 4, medetomidine (Dorbene vet, Zoetis Deutschland GmbH, Germany) was initially given as a bolus loading dose, followed by a gradual reduction of isoflurane and its eventual discontinuation 10 min later; continuous infusion of medetomidine commenced 15 min after the bolus.

    Techniques: Produced, Construct