Axonal Outgrowth and Erk1/2 Activation by Training after Spinal Cord Injury in Rats

Physical training in experimental animals can improve locomotor activity via the regulation of spinal neural circuitry or peripheral nerve regeneration. Here we investigated the effects of treadmill training (TMT) on regenerative responses of the corticospinal tract (CST) after contusive spinal cord injury (SCI). One week after injury of the low thoracic spinal cord, rats were given TMT or sedentary treatment for 1-4 weeks. Anterograde tracing of descending CST axons revealed that TMT enhanced collateral arborization of CST axons surrounding the injury cavity and promoted extension into the caudal spinal cord. The number of oligodendrocytes in the vicinity of the injury cavity was significantly increased at 2 or 4 weeks after TMT compared to sedentary controls. The data further showed that TMT increased phosphorylation of Erk1/2 in the motor cortex as well as the spinal cord injury area, and inhibition of Erk1/2 activity by administration of the MEK1 inhibitors PD98059 and U0126 reduced collateral outgrowth of descending CST axons in TMT animals. TMT for 2-4 weeks significantly improved behavioral scores as assessed by the Basso-Beattie-Bresnahan scale, as well as on motor function and gridwalk testing. Our data imply that Erk1/2 may be an important mediator for transmitting signals from the injury site to the cell body, and further suggest that activation of the Erk1/2 signaling pathway may be involved in enhanced outgrowth of CST axons after TMT.