Combination of NEP 1-40 Treatment and Motor Training Enhances Behavioral Recovery after a Focal Cortical Infarct in Rats

Background and Purpose: Although myelin-associated neurite outgrowth disinhibitors have shown promise in restoring motor function after stroke, their interactive effects with motor training have rarely been investigated. The present study examined whether a combinatorial treatment (NEP 1-40+motor rehabilitation) is more effective than either treatment alone in promoting motor recovery after focal ischemic injury. Methods: Adult rats were assigned to one of 3 treatment groups (infarct/NEP 1-40+motor training, infarct/NEP 1-40 only, infarct/motor training only) and 2 control groups (infarct/no treatment, intact/no treatment). A focal ischemic infarct was induced by microinjecting endothelin-1 into the motor cortex. Therapeutic treatments were initiated 1 week postinfarct and included intraventricular infusion of the pharmacological agent NEP 1-40 and motor training (skilled reach task). Behavioral assessments on skilled reach, foot fault, and cylinder tests were conducted before the infarct and for 5 weeks postinfarct. Results: Rats demonstrated significant forelimb impairment on skilled reach and foot fault tests after the infarct. Although all infarct groups improved over time, motor training alone and NEP 1-40 alone facilitated recovery on the skilled reach task at the end of treatment Weeks 2 and 4, respectively. However, only NEP 1-40 paired with motor training facilitated recovery after 1 week of treatment in addition to treatment at Weeks 2 and 4. Finally, only the NEP 1-40+motor training group maintained a performance level equivalent to that of the intact group over the entire period of posttreatment assessment. Conclusions:s: This study suggests that behavioral training interacts with the effects of the axonal growth promoter, NEP 1-40, and may accelerate behavioral recovery after focal cortical ischemia.