Continuous intrathecal infusion of SB203580, a selective inhibitor of p38 mitogen-activated protein kinase, reduces the damage of hind-limb function after thoracic spinal cord injury in rat

Abstract

P38 mitogen-activated protein kinase (MAPK) is one of the key enzymes in apoptosis induction pathways. We tested continuous intrathecal infusion of SB203580, a selective inhibitor of p38-MAPK, after spinal cord compression injury by a 20 g weight for 40 min at the 11th vertebra level-thoracic spinal cord. SB203580 (1 μg/day) was infused for 1 week after the compression. Hind-limb function was evaluated by measuring the frequency of ‘standing’ posture; raising fore limbs and sustaining body weight with hind-limbs. One-week after the compression, frequency of standing spinal cord injured rat was decreased to about half of that in sham operated animals which underwent laminectomy without compression. The frequency of standing in rats infused SB203580 recovered 2–3 weeks after the spinal cord injury, on the other hand, vehicle animals infused with saline did not recover. Myelin staining by Luxol fast blue showed severe myelin degradation in vehicle animals in lateral and dorsal funiculi. Apoptotic cells, detected by TUNEL staining, appeared in lateral funiculi of spinal cord injured rats. The application of SB203580 decreased the number of apoptotic cells. The SB203580-treated animals showed no significant degeneration of myelin structure. These results suggest that inhibition of p38-MAPK is one candidate for therapeutic agents against neurological deficits after spinal cord injury.