Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study

Area of Science:

• Neuroscience
• Pharmacology
• Stroke Research

Background:

• Ischemic stroke treatment is limited to tissue plasminogen activator, with a narrow therapeutic window.
• Progesterone has demonstrated preclinical benefits in stroke models, but dose-response and time-window data are lacking.

Purpose of the Study:

• To investigate the dose-response relationship of progesterone in a rat model of ischemic stroke.
• To determine the optimal therapeutic time window for progesterone administration after stroke onset.

Main Methods:

• Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion.
• Progesterone was administered at varying doses (8, 16, 32 mg/kg) and time points (3, 6, 24 hours post-stroke).
• Behavioral recovery and infarct volume were assessed up to 22 days post-stroke.

Main Results:

• Doses of 8 and 16 mg/kg progesterone significantly reduced infarct volume and improved functional outcomes (locomotor activity, grip strength, sensory neglect, gait, coordination, spatial navigation).
• Progesterone administration up to 6 hours post-stroke demonstrated significant neuroprotection and reduced infarct size.
• The 8 mg/kg dose was optimal for improving motor, sensory, and memory functions within a broad therapeutic window.

Conclusions:

• Moderate doses of progesterone effectively reduce infarct size and improve functional deficits in a clinically relevant ischemic stroke model.
• Progesterone exhibits a promising therapeutic potential for ischemic stroke, warranting clinical trials for safety and efficacy.