Evaluation of a motor deficit after chronic focal cerebral ischemia in rats

Abstract

It is well known that hemiplegia is frequently observed in cerebral ischemia. It is important for the pathophysiologic study and development of drug therapies to establish a precise method investigating impairment of motor function with animal models. To develop a quantitative and objective method for evaluating impairment of motor function, we examined an inclined plane test after chronic focal cerebral ischemia in the rat. Standard scoring of neurologic deficits has limitations, including problems with quantification and objectivity. The purpose of this study was to establish a novel method for evaluating impairment of motor function in middle cerebral artery (MCA) occluded rats. The left MCA was permanently occluded at a proximal site, and sensorimotor performance was evaluated at the fifth day and every week for 11 weeks thereafter. The ability to maintain body position on an inclined plane was measured when rats were placed on a stainless steel slope in left-headed, right-headed, and up-headed positions. Neurologic examination based on hemiparesis and abnormal posture was also performed. After all behavioral examinations were completed, the degree of shrinkage of the left hemisphere to the contralateral was measured. The ability of MCA-occluded rats to maintain position on an inclined plane in the left-headed position was significantly restricted when compared with that of sham-operated rats throughout the test period (maximum angle of 37 degrees versus 45 degrees, respectively). Minimal natural recovery was observed for all position measurements. MCA-occluded rats showed a significantly higher neurologic score with natural recovery. The ability to maintain position on an inclined plane after MCA occlusion (MCAO) was significantly correlated with the degree of the shrinkage of the ischemic hemisphere and neurologic score. The angle for the left-headed position was most strongly correlated with ipsilateral shrinkage. In the present study, long-lasting impairment of motor function was detected in rats with MCAO, which correlated with the shrinkage of the ischemic hemisphere. Furthermore, a difference in performance depending on body position (left-headed versus right-headed) was also detected. The left-headed position was found to be most sensitive for evaluating this model. The inclined plane test is a quantitative, objective, and sensitive method for evaluating motor deficits after chronic focal cerebral ischemia in rats, and this method may be useful to investigate changes in motor function in hemiplegia.