Dataset DOI: 10.5061/dryad.95x69p900

Description of the data and file structure

Aim 1: Healthy, male, wild-type mice were administered Lemborexant (10 mg/kg, N = 7), Lemborexant (30 mg/kg, N = 7), Zolpidem (30 mg/kg, N = 7), or vehicle (N = 7) via Jell-O in a randomized order, with a three-day washout period between each dose. EEG/EMG signals were recorded continuously, and the 24-hour period following each dose was scored for NREM, REM, and Wake states. Analyses included vigilance-state quantification, EEG power, sleep fragmentation, sleep latency, and circadian index.

Aim 2: Photothrombotic stroke was induced in male, wild-type mice, which were then given a single dose of Lemborexant (10 mg/kg, N = 13), Lemborexant (30 mg/kg, N = 14), Zolpidem (30 mg/kg, N = 12), or vehicle (N = 16) via Jell-O. EEG/EMG signals were recorded continuously, and the subsequent 24-hour period was scored for NREM, REM, and Wake states. Analyses included vigilance-state quantification, EEG power, sleep fragmentation, sleep latency, and circadian index.

Aim 3: Photothrombotic stroke was induced in male, wild-type mice, which then underwent a 12-day dosing regimen of Lemborexant (10 mg/kg, N = 7), Lemborexant (30 mg/kg, N = 7), Zolpidem (30 mg/kg, N = 7), or vehicle (N = 7). Behavioral tests assessing asymmetry during exploratory behavior were conducted before stroke induction and again at 48 hours, 2 weeks, 4 weeks, and 8 weeks post-stroke. At the 8-week time point, mice were sacrificed and infarct volume was quantified.

Files and variables

File: Figure_1_KMI.prism

Description: For all data tables in Figure 1, the independent variables are the four drug types the mice received in a randomized order in aim 1 of the study: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). For "A1 NREM_3hr" and "A1 REM_3hr", the total duration of NREM and REM, respectively, is reported for the first three hours after drug administration as a percentage. "A1 NREM Latency" and "A1 REM Latency" represent the time until the first NREM or REM bout, respectively, post-drug administration. "A1 #Arousal_3hr" represents the number of arousals (events) within the first three hours post-drug administration; arousals were defined as transitions from NREM or REM to Wake lasting less than 300 seconds. "A1 meanREM_3hr" and "A1 meanNREM_3hr" represent the mean bout duration of REM and NREM, in minutes, within the first three hours post-drug administration. "Aim 1 Circadian Index" represents the circadian index of wakefulness for the 24 hours post-drug administration. Circadian index of wakefulness was calculated using the following formula: CI = (Percent Wake Dark Period – Percent Wake Light Period) / Percent Wake 24-Hour.

"A1 PSD NREM," "A1 PSD REM," and "A1 PSD Wake" are power spectral density arrays depicting the effect of the four drug types on the EEG power of each vigilance state within the first three hours post-drug administration. Power values were plotted on a logarithmic scale.

File: Figure_2_KMI.prism

Description: For all data tables in Figure 2, the independent variables are the four drugs each group of mice received after undergoing photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "A2 NREM_3hr" and "A2 REM_3hr" quantify the change in total duration, in percentage, of NREM and REM sleep, respectively, from 48–51 hours post-stroke to 72–75 hours post-stroke (first three hours post-drug administration). "NREM Latency (Normalized)" and "REM Latency (Normalized)" represent the change in time to the first NREM or REM bout, respectively, from 48–51 hours post-stroke to 72–75 hours post-stroke. "#Arousal_3hr" represents the change in number of arousals (events)—defined as transitions from NREM or REM to Wake lasting less than 300 seconds—from 48–51 hours post-stroke to 72–75 hours post-stroke. "meanNREM_3hr" and "meanREM_3hr" represent the change in bout duration, in minutes, of NREM and REM, respectively, across the same time periods. "Aim 2 Change in Circadian Index" represents the change in circadian index of wakefulness (calculated using the formula described in Figure 1) from 48–72 hours post-stroke to 72–96 hours post-stroke.

File: Figure_3_KMI.prism

Description: For all data tables in Figure 3, the independent variables are the four drugs each group of mice received daily during the 12-day dosing period in aim 3: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). Each group started with N = 16 mice, but several were excluded due to not having a stroke or not reaching the end of the study. The blank cells in some drug groups reflect these exclusions. "Infarct Volume" represents the stroke volume (µm³) in each mouse 8 weeks post-stroke following cresyl violet staining. "MD-2wk Score all groups," "MD-4wk Score all groups," and "MD-8wk Score all groups" represent the change in forelimb asymmetry score from a stroke-sensitive behavior test called cylinder rearing, from Max Deficit (48 hours post-stroke) to 2 weeks, 4 weeks, and 8 weeks post-stroke, respectively. Asymmetry score was calculated as percent difference in left vs. right forelimb use during rearing: ((left rears – right rears) / (left rears + right rears + both forepaw rears)) × 100.

File: Supplementary_Figure_1_KMI.prism

Description: For all data tables in Supplementary Figure 1, the independent variables are the four drug types the mice received in a randomized order in aim 1: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "A1 REM TimeCourse" and "A1 NREM TimeCourse" indicate the total duration of REM and NREM, respectively, as a percentage of hours elapsed over the 24 hours post-drug administration and depict drug effects across light and dark cycles. "A1 NREM_24hr" and "A1 REM_24hr" represent the total duration of NREM and REM, as a percentage of the 24-hour period post-drug administration.

File: Supplementary_Figure_2_KMI.prism

Description: For all data tables in Supplementary Figure 2, the independent variables are the four drug types the mice received in a randomized order in aim 1: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "A1 #Arousal_24hr" represents the number of arousals (events) across the 24 hours post-drug administration; arousals were defined as transitions from NREM or REM to Wake lasting less than 300 seconds. "A1 MeanNREM_24hr" and "A1 meanREM_24hr" represent mean bout duration of NREM and REM, in minutes, across the same 24-hour period.

File: Supplementary_Figure_3_KMI.prism

Description: For all data tables in Supplementary Figure 3, the independent variables are the four drug types the mice received in a randomized order in aim 1: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). The data tables provide further analysis of the power spectral density arrays in Figure 1. To summarize spectral shape, we calculated spectral slope/exponent as the regression coefficient of the log–log PSD fit and spectral offset as the y-intercept. "A1 Exponent NREM," "A1 REM Exponent," and "A1 Exponent Wake" represent slopes of the EEG power spectral density arrays from Figure 1, and "A1 Offset NREM," "A1 Offset REM," and "A1 Offset Wake" represent the corresponding y-intercepts.

File: Supplementary_Figure_4_KMI.prism

Description: For all data tables in Supplementary Figure 4, the independent variables are the four drugs each group of mice received after photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "A2 NREM_3hr (absolute)" and "A2 REM_3hr (absolute)" represent the total duration of NREM and REM, as a percentage, during 72–75 hours post-stroke. "NREM Latency (absolute)" and "REM Latency (absolute)" represent the time in minutes to the first NREM or REM bout, respectively, within 72–75 hours post-stroke.

File: Supplementary_Figure_5_KMI.prism

Description: For all data tables in Supplementary Figure 5, the independent variables are the four drugs each group of mice received after photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "A2 NREM_24hr" and "A2 REM_24hr" quantify the change in total duration, in percentage, of NREM and REM sleep, respectively, from 48–72 hours post-stroke to 72–96 hours post-stroke. "A2 NREM Time Course" and "A2 REM Time Course" indicate the total duration of NREM and REM, as a percentage of hours elapsed over 72–96 hours post-stroke, and depict drug effects across light and dark cycles.

File: Supplementary_Figure_6_KMI.prism

Description: For all data tables in Supplementary Figure 6, the independent variables are the four drugs each group of mice received after photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "#Arousal_3hr (absolute)" represents the number of arousals (events) during 72–75 hours post-stroke; arousals were defined as transitions from NREM or REM to Wake lasting less than 300 seconds. "meanNREM_3hr (absolute)" and "meanREM_3hr (absolute)" represent mean bout duration, in minutes, of NREM and REM, respectively, during 72–75 hours post-stroke.

File: Supplementary_Figure_7_KMI.prism

Description: For all data tables in Supplementary Figure 7, the independent variables are the four drugs each group of mice received after photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "#Arousal_24hr" quantifies the change in number of arousals (events) from 48–72 hours post-stroke to 72–96 hours post-stroke. Arousals were defined as transitions from NREM or REM to Wake lasting less than 300 seconds. "meanNREM_24hr" and "meanREM_24hr" quantify the change in mean bout duration, in minutes, of NREM and REM, respectively, across the same periods.

File: Supplementary_Figure_8_KMI.prism

Description: For all data tables in Supplementary Figure 8, the independent variables are the four drugs each group of mice received after photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). "Aim 2 72–96 Hr Circadian Index" represents the circadian index of wakefulness for hours 72–96 post-stroke (calculated using the formula from Figure 1).

File: Supplementary_Figure_9_KMI.prism

Description: For all data tables in Supplementary Figure 9, the independent variables are the four drugs each group of mice received after photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). The files within Supplementary Figure 9 are separated by drug group and vigilance state. They contain EEG power spectral density arrays comparing effects of drug at 72–75 hours post-stroke to baseline 48–51 hours post-stroke for each vigilance state.

File: Supplementary_Figure_10_KMI.prism

Description: For all data tables in Supplementary Figure 10, the independent variables are the four drugs each group of mice received after photothrombotic stroke in aim 2: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). The data tables provide further analysis of the power spectral density arrays in Supplementary Figure 9. To summarize spectral shape, we calculated spectral slope/exponent as the regression coefficient of the log–log PSD fit and spectral offset as the y-intercept. "A2 Exponent NREM," "A2 Exponent REM," and "A2 Exponent Wake" quantify the change in slope of the EEG power spectral density arrays from Supplementary Figure 9 from 48–51 hours post-stroke to 72–75 hours post-stroke. "A2 Offset NREM," "A2 Offset REM," and "A2 Offset Wake" quantify the change in y-intercept of the PSDs across the same periods.

File: Supplementary_Figure_11_KMI.prism

Description: For all data tables in Supplementary Figure 11, the independent variables are the four drugs each group of mice received daily during the 12-day dosing period in aim 3: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). Each group began with N = 16 mice, but several were excluded due to not having a stroke or not reaching the end of the study. The blank cells reflect these exclusions. "STI" represents the prevalence, in percentage, of Secondary Thalamic Injury within each drug group.

File: Supplementary_Figure_12_KMI.prism

Description: For all data tables in Supplementary Figure 12, the independent variables are the four drugs each group of mice received daily during the 12-day dosing period in aim 3: Vehicle (VEH), Zolpidem 30 mg/kg (ZOL30), Lemborexant 10 mg/kg (LEM10), and Lemborexant 30 mg/kg (LEM30). Each group began with N = 16 mice, but several were excluded due to not having a stroke or not reaching the end of the study. The blank cells reflect these exclusions. "MD-2wk Score all groups," "MD-4wk Score all groups," and "MD-8wk Score all groups" quantify the change in asymmetry score from the Y-maze behavior test. Asymmetry scores were calculated as the change in percentage of leftward head turns relative to total head turns from baseline (24 hours post-stroke) to two, four, and eight weeks post-stroke.

Code/software

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