Effect of FK-506 on inflammation and behavioral outcome following intracerebral hemorrhage in rat

Beginning 15 min after induction of intracerebral hemorrhage (ICH) by intra striatal administration of collagenase, rats were treated intramuscularly w ith FK-506 (3 mg/kg) or with vehicle. Treatment was repeated daily for 7 da ys. MR imaging 1, 7, and 28 days post-ICH showed that treatment did not aff ect hematoma size or its subsequent resolution. Two days post-ICH, neutroph il infiltration around the hematoma was decreased in the FK-506-treated rat s, as was the number of TUNEL-positive cells at the edge of the hematoma an d in the peripheral region. The decreased inflammatory response was accompa nied by functional improvement in the treated rats. The neurological defici t induced by the ICH (beam walking ability, postural reflex, spontaneous ci rcling) was significantly decreased from 3 to 21 days post-ICH by treatment with FK-506. Skilled use of the forelimb ipsilateral to the ICH was improv ed and sensory neglect of the same limb was decreased 8-9 weeks post-ICH in rats treated with FK-506. However, neuronal loss assessed 9 weeks post-ICH was not different in the treated and untreated rats. (C) 2000 Academic Pre ss.