A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats

Background and Purpose-Proven behavioral assessment strategies for testing potential therapeutic agents in rat stroke models are needed. Few studies i nclude tasks that demand higher levels of sensorimotor and cognitive functi on. Because behavioral outcome and rate of recovery vary among ischemia mod els, there is a need to characterize and compare performance on specific ta sks across models. Methods-To this end, sensorimotor and cognitive deficits were assessed duri ng a 5-week period after either permanent proximal middle cerebral artery o cclusion (pMCAO) or permanent distal middle cerebral artery occlusion combi ned with a 90-minute occlusion of both common carotid arteries (dMCAO/tCCAO ) in Sprague-Dawley rats. The EBST, hindlimb and forelimb placing, and cyli nder tests were given at regular intervals postinjury to assess sensorimoto r function. Cognitive function was assessed with a multitrial water navigat ion task. Results-pMCAO, which caused both striatal and cortical damage, produced per sistent sensormotor and cognitive deficits. Limb placing responses and post ural reflexes were impaired throughout the month of testing. A persistent b ias for using the ipsilateral forelimb for wall movements in the cylinder t est was observed as well as a bias for landing on the opposite forelimb. pM CAO rats were also impaired in the water navigation task. dMCAO/tCCAO, whic h caused only cortical damage, produced similar sensorimotor deficits, but these were greatly diminished by 2 weeks after injury. No impairment was fo und for water tank navigation. Correlations between forelimb placing (both models), water navigation performance (pMCAO model), and sensorimotor asymm etry (dMCAOtCCAO model) and infarct volume were observed. Conclusions-Based on the range of functions affected and stability of obser ved deficits, the pMCAO model appears to be preferable to the dMCAO/tCCAO m odel for use in assessing therapeutic agents for stroke.