Source Paper
Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study
Bushra Wali, Tauheed Ishrat, Soonmi Won, Donald G. Stein, Iqbal Sayeed
Brain • 2013
Source Paper
Bushra Wali, Tauheed Ishrat, Soonmi Won, Donald G. Stein, Iqbal Sayeed
Brain • 2013
Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke.
Objective: Assessment of sensory neglect to measure sensory deficits following permanent middle cerebral artery occlusion (stroke) in rats
This is a Sensory Neglect Test protocol using rat as the model organism. The procedure involves 8 procedural steps, 6 equipment items, 2 materials. Extracted from a 2013 paper published in Brain.
Model and subjects
rat • Sprague-Dawley • male • 12 months old
Study window
~3.1 week study window | ~110 hours hands-on
Core workflow
Surgical procedure - Permanent middle cerebral artery occlusion or sham operation • Dose-response study - Initial progesterone injection • Dose-response study - Subcutaneous injections at 6 hours
Primary readouts
Key equipment and reagents
Verified items
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Male Sprague-Dawley rats (12 months old) underwent either permanent middle cerebral artery occlusion or sham operations
Note: This creates the stroke model for testing
“We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance”
Animals received intraperitoneal injections of progesterone at 1 hour post-occlusion
Note: Three dose levels tested: 8, 16, or 32 mg/kg
“For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion”
Animals received subcutaneous injections of progesterone at 6 hours post-occlusion
Note: Same dose levels as initial injection
“subcutaneous injections at 6 h and then once every 24 h for 7 days”
Animals received subcutaneous injections once every 24 hours for 7 days following the 6-hour injection
Note: Continuation of treatment regimen
“subcutaneous injections at 6 h and then once every 24 h for 7 days”
In the time-window study, the optimal dose of progesterone was given starting at 3, 6, or 24 hours post-stroke
Note: Optimal dose determined from dose-response study
“For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke”
Rats were tested on sensory neglect test to measure sensory deficits following stroke
Note: Part of comprehensive behavioral assessment battery
“Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume”
Rats were tested on grip strength, gait impairment, motor coordination, and spatial navigation tests
Note: Comprehensive functional outcome measures
“improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests”
Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume
Note: Terminal endpoint for anatomical assessment
“Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
Assessment of sensory neglect to measure sensory deficits following permanent middle cerebral artery occlusion (stroke) in rats
Objective
Assessment of sensory neglect to measure sensory deficits following permanent middle cerebral artery occlusion (stroke) in rats
Subjects
From paperrat • Sprague-Dawley • male • 12 months old
Cohort notes
From paperAnimals underwent permanent middle cerebral artery occlusion or sham operations
Surgical procedure - Permanent middle cerebral artery occlusion or sham operation
Dose-response study - Initial progesterone injection (1 hour post-occlusion)
Dose-response study - Subcutaneous injections at 6 hours (6 hours post-occlusion)
Dose-response study - Repeated subcutaneous injections (Once every 24 hours for 7 days)
Sensory neglect (sensory deficit assessment)
From paperNot explicitly described in the provided text
Artifact type
Longitudinal gait metrics and per-animal performance tables
Comparison focus
Compare recovery trajectory across post-injury timepoints and treatment conditions
Infarct volume
From paperNot explicitly described in the provided text
Artifact type
Longitudinal gait metrics and per-animal performance tables
Comparison focus
Compare recovery trajectory across post-injury timepoints and treatment conditions
Locomotor activity
From paperNot explicitly described in the provided text
Artifact type
Longitudinal gait metrics and per-animal performance tables
Comparison focus
Compare recovery trajectory across post-injury timepoints and treatment conditions
Grip strength
From paperNot explicitly described in the provided text
Artifact type
Longitudinal gait metrics and per-animal performance tables
Comparison focus
Compare recovery trajectory across post-injury timepoints and treatment conditions
Sensory neglect (sensory deficit assessment)
From paperRaw artifact
Per-run gait capture with paw placement, timing, and stride features for each animal
Processed artifact
Cleaned gait metrics table and recovery trend summary across timepoints
Final reported form
Group comparisons of gait indices, stride metrics, or recovery curves
Infarct volume
From paperRaw artifact
Per-run gait capture with paw placement, timing, and stride features for each animal
Processed artifact
Cleaned gait metrics table and recovery trend summary across timepoints
Final reported form
Group comparisons of gait indices, stride metrics, or recovery curves
Locomotor activity
From paperRaw artifact
Per-run gait capture with paw placement, timing, and stride features for each animal
Processed artifact
Cleaned gait metrics table and recovery trend summary across timepoints
Final reported form
Group comparisons of gait indices, stride metrics, or recovery curves
Grip strength
From paperRaw artifact
Per-run gait capture with paw placement, timing, and stride features for each animal
Processed artifact
Cleaned gait metrics table and recovery trend summary across timepoints
Final reported form
Group comparisons of gait indices, stride metrics, or recovery curves
Acquisition
Capture run-level gait data for each animal and preserve the timepoint or treatment labeling.
Preprocessing / cleaning
Not explicitly described in the provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Sensory neglect (sensory deficit assessment); Infarct volume; Locomotor activity; Grip strength.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Sensory neglect (sensory deficit assessment), Infarct volume, Locomotor activity, Grip strength.
Source links and direct wording from the methods section for validation and deeper review.
Citation
Bushra Wali et al. (2013). Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study. Brain
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