Collagenase-Induced Intrastriatal Hemorrhage in Rats Results in Long-term Locomotor Deficits

Abstract

Background and Purpose Previous studies have shown that injection of the metalloproteinase collagenase directly into the caudate nucleus of rats causes an intracerebral hemorrhage. The purpose of the present study is to determine functional deficits associated with a collagenase-induced hemorrhagic lesion of the striatum. Methods Twelve adult rats received a 2-μL infusion of bacterial collagenase (0.5 U in saline) into the right striatum. The rotational response to apomorphine (1 mg/kg SC) administration was then examined at 1, 4, 7, 21, 35, and 70 days after the surgery. In addition to the rotational asymmetry studies, the initiation of stepping movements in each forelimb was determined 8 weeks after the collagenase injections. In the assessment of rotational asymmetry and stepping ability, an additional six control animals received unilateral injections of saline alone. After behavioral testing, brains were processed for neuropathological evaluation. Results A net ipsilateral rotation was noted at all posthemorrhage time periods. The average rotational asymmetries on these days were 14.57±2.9, 20.33±2.7, 19.99±4.4, 18.95±4.9, 17.03±4.9, and 14.4±4.7, respectively (data expressed as mean clockwise rotations per 5 minutes ±SEM). The average number of steps initiated by the forelimb ipsilateral and contralateral to the lesion was 28.3±2.1 steps per minute and 13.6±1.5 steps per minute, respectively. This difference between left and right forelimb stepping was stable and reproducible for 3 consecutive days. Histological studies revealed a long-lasting hematoma cavity surrounded by dense reactive gliosis in the striatum. Conclusions We conclude that collagenase-induced intrastriatal hemorrhage results in long-term locomotor deficits and is therefore a useful model for developing and assessing therapeutic approaches for the restoration of neurological function after intracerebral hemorrhage.