Affiliations: Department of Emergency Medicine, Brain Research
Laboratory, Emory University, Atlanta, GA 30322, USA
Note: [] Corresponding author: Donald G. Stein, Ph.D., Emory University
School of Medicine, 1365 B Clifton Road, Suite 5100, Atlanta, GA 30322, USA.
Tel.: +1 404 712 9704; Fax: +1 404 727 2388; E-mail: dstei04@emory.edu
Abstract: Purpose: Previous studies suggest that progesterone (PROG) has a
substantial protective effect against several types of brain injury. Since most
cases of human stroke are caused by permanent occlusion of cerebral arteries,
we assessed the neuroprotective effects of PROG on cerebral infarction and
behavioral deficits in a permanent MCAO (pMCAO) model. Methods: pMCAO was
produced by surgical insertion of a silicone-coated nylon filament into the
right internal carotid artery. Laser-Doppler flowmetry was used to monitor
cerebral blood flow for 10 min post-occlusion. PROG (8 mg/kg) or vehicle
(2-hydroxypropyl-β-cyclodextrin) was administered intraperitoneally at
1 h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h
post-occlusion. Measurements of infarct volumes (cortical, subcortical and
total) were performed at 72 h and functional recovery, assessed by rotarod
test, were performed 24, 48, and 72 h after pMCAO. Results: Following
PROG treatment, stained sections revealed a significant reduction in cortical,
caudate-putamen and hemispheric infarct volumes (% contralateral structure)
compared to vehicle-injected controls. In addition, PROG treatment reduced
functional deficits on the accelerating rotarod apparatus. Conclusion: We
demonstrated and confirmed the neuroprotective effect of PROG using a permanent
model of focal brain ischemia in rats.
