Abstract T P68: Delayed Progesterone Treatment Improves Long-Term Recovery of Function Following Permanent Stroke in Older Rats

Abstract

BACKGROUND: Less is known about the long-term sustained effects of PROG on recovery of function following stroke. Two objectives were evaluated, First, whether functional deficits caused by pMCAO persist and if repeated testing in itself reduce the extent of injury over long periods (8 weeks). Second, determine PROG's effects on a panel of behavioral tests performed several weeks post-pMCAO Methods: Male Sprague-Dawley rats (12 months old) underwent pMCAO by electrocoagulation or sham surgery. For the first study, repeated long term group with pMCAO began a battery of tests at repeated intervals (during the 3rd, 6th, and 8th weeks post-pMCAO), while long term with pMCAO group testing began during the 8 th week post-pMCAO. For the second study, beginning 3 h post-occlusion, rats were given IP injections of 8 mg/kg of PROG or vehicle, followed by SC injections at 8 h and then every 24 h for 9 days with tapering of final 2 treatments. All animals received: motor, sensory and cognitive tests; grip strength, rotarod, sensory neglect tests and spatial navigation learning and memory test; and computerized analysis of gait impairment. Results: Functional deficits caused by pMCAO showed modest improvement over time but were still persistent in older rats. Repeated testing (3 times over 8 weeks) did not reduce the effects of injury. Despite modest recovery in vehicle treated rats at eight weeks post-pMCAO, PROG treatment given 3 h after stroke and compared with vehicle group, showed improvement in grip strength by 59.28%, rotarod stability by 46.36 %, reduced sensory neglect by 28.69% and memory deficits by 38.56%. Automated gait assessment showed that PROG treatments significantly improved motor deficits in the affected limb on parameters like stride length, strand, paw print, and swing cycle. Conclusions: 1. The above tested behavioral assays over long-term assessment period, can be used for evaluating therapeutic agents in models of ischemic stroke in older rats. 2 . PROG was found to have sustained effect up to 8 weeks post stroke. PROG shows pre-clinical promise and should be examined for safety and efficacy in a clinical trial for ischemic stroke.