Abstract
We have developed internal capsule (IC) hemorrhage model rats by injection of collagenase (1.4 μl of 7.5 U/ml in saline) into the striatum near the IC, which had a small hematoma but relatively bigger motor dysfunction caused by rapid degeneration of myelin and axon in the IC within the first 24 hours after the lesion. To investigate whether iron was involved in pathological mechanism in early-phase after intracerebral hemorrhage, an iron chelator, clioquinol (CQ: 100 mg/kg/day orally) was daily administrated to IC model rats from 7 days before (pre-treatment) or from 6 hours after (post-treatment) the lesion to 7 days after the lesion. Behavioral test showed that pre-treatment of CQ significantly reduced the motor dysfunction 7 days after the lesion as compared with vehicle-treatment. However, post-treatment of CQ have not a significance but a tendency to reduce the motor dysfunction after the lesion. Retrograde labeling of neurons in sensorimotor cortex at 14 days after the lesion by Fluoro-Gold injection (corticospinal tract at C3-C4 level) showed that there were more labeled neurons in pre-treatment group (n=4; 57.2 ± 16.5% of contralateral side, 0.7 mm anterior to the bregma) compared to those in vehicle-treatment group (n=6; 14.7 ± 12.7%). Data suggested that inhibition of iron accumulation by clioquinol treatment attenuated motor dysfunction by protecting the damage of corticospinal tract after ICH, probably mediated by reduction of hydroxyl radical from catalytic chain reaction by iron. [Jpn J Physiol 55 Suppl:S174 (2005)]
