Progesterone in transient ischemic stroke: a dose–response study

• Published in: Psychopharmacology 2014-09, Vol.231 (17), p.3313-3323
• Main Authors: Yousuf, Seema, Atif, Fahim, Sayeed, Iqbal, Tang, Huiling, Stein, Donald G.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Dosage and administration; Dose-Response Relationship, Drug; Drug interactions; Drug therapy; Gait Disorders, Neurologic - drug therapy; Hand Strength; Identification and classification; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - psychology; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - pathology; Ischemic Attack, Transient - psychology; Male; Maze Learning - drug effects; Memory; Memory - drug effects; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - therapeutic use; Neurosciences; Original Investigation; Perceptual Disorders - drug therapy; Perceptual Disorders - psychology; Pharmacology/Toxicology; Postural Balance - drug effects; Progesterone; Progesterone - administration & dosage; Progesterone - therapeutic use; Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Steroids; Stroke; Stroke (Disease)
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-014-3556-8

Rationale Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking. Objectives We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats. Methods Cerebral ischemia was induced in 13-month-old male Sprague–Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke. Results Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved ( p