A Model of Persistent Learned Nonuse Following Focal Ischemia in Rats. (November 2013) - MacLellan, Crystal L.
Background . After hemiplegic stroke, people often rely on their unaffected limb to complete activities of daily living. A component of residual motor dysfunction involves learned suppression of movement, termed learned nonuse. Objective . To date, no rodent stroke model of persistent learned nonuse has been described that can facilitate understanding of this phenomenon and test interventions to overcome it. Methods . Rats were trained in the staircase skilled-reaching and limb use asymmetry (cylinder) tasks. Endothelin-1 was injected into the cortex and striatum to create focal ischemia. Starting 7 days poststroke, half of the rats (ipsilateral training; n = 15) were trained to reach for food reward pellets in the tray-reaching task with the ipsilateral forelimb. Training lasted 20 days. Rats in the control group (control; n = 15) did not receive training. All rats then remained in their home cages for an additional 30 days. Performance on the cylinder and staircase tasks was assessed ~2 months poststroke. Results . Ischemia caused significant functional impairments in all rats. Significant contralateral forelimb skilled-reaching recovery was evident in the control group at 2 months but not the ipsilateral training group. There was no difference in performance in the cylinder task. Similarly, the volume of brain injury (~66 mm 3 ) was similar between groups. Ipsilateral forelimb training reduced poststroke motor recovery. Conclusion . This rodent model of persistent nonuse after stroke may be used to further understand mechanisms of learned nonuse as well as to evaluate pharmacological and rehabilitation treatments to overcome it.