title: Progesterone improves long-term functional and histological outcomes after permanent stroke in older rats.
abstract: Previous studies have shown progesterone to be beneficial in animal models of central nervous system injury, but less is known about its longer-term sustained effects on recovery of function following stroke. We evaluated progesterone's effects on a panel of behavioral tests up to 8 weeks after permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats 12m.o. were subjected to pMCAO and, beginning 3h post-pMCAO, given intraperitoneal injections of progesterone (8mg/kg) or vehicle, followed by subcutaneous injections at 8h and then every 24h for 7 days, with tapering of the last 2 treatments. The rats were then tested on functional recovery at 3, 6 and 8 weeks post-stroke. We observed that progesterone-treated animals showed attenuation of infarct volume and improved functional outcomes at 8 weeks after stroke on grip strength, sensory neglect, motor coordination and spatial navigation tests. Progesterone treatments significantly improved motor deficits in the affected limb on a number of gait parameters. Glial fibrillary acidic protein expression was increased in the vehicle group and considerably lowered in the progesterone group at 8 weeks post-stroke. With repeated post-stroke testing, sensory neglect and some aspects of spatial learning performance showed spontaneous recovery, but on gait and grip-strength measres progesterone given only in the acute stage of stroke (first 7 days) showed sustained beneficial effects on all other measures of functional recovery up to 8 weeks post-stroke.
authors.affiliation: Department of Emergency Medicine, Brain Research Laboratory, Emory University, Atlanta, GA, USA. Electronic address: bwali@emory.edu.
authors.forename: Bushra
authors.initials: B
authors.lastname: Wali
authors.affiliation: Department of Emergency Medicine, Brain Research Laboratory, Emory University, Atlanta, GA, USA. Electronic address: TISHRAT@gru.edu.
authors.forename: Tauheed
authors.initials: T
authors.lastname: Ishrat
authors.affiliation: Department of Emergency Medicine, Brain Research Laboratory, Emory University, Atlanta, GA, USA. Electronic address: dstei04@emory.edu.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stein
authors.affiliation: Department of Emergency Medicine, Brain Research Laboratory, Emory University, Atlanta, GA, USA. Electronic address: isayeed@emory.edu.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Sayeed
mesh_terms: D000375:Aging; D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D020233:Gait Disorders, Neurologic / Q000188:drug therapy* / Q000209:etiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D053580:Muscle Strength / Q000187:drug effects; D010468:Perceptual Disorders / Q000188:drug therapy / Q000209:etiology; D011374:Progesterone / Q000494:pharmacology / Q000627:therapeutic use*; D011372:Progestins / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D011372:Progestins; D011374:Progesterone
keywords: Functional recovery; Long-term functional deficit; Permanent stroke; Progesterone; Stroke