Background
Motor rehabilitative training improves behavioral functionality and promotes beneficial neural reorganization following stroke but is often insufficient to normalize function. Rodent studies have relied on skilled reaching tasks to model motor rehabilitation and explore factors contributing to its efficacy. It has been found that greater training intensity (sessions/day) and duration (training days) facilitates motor skill learning in intact animals. Whether rehabilitative training efficacy varies with intensity following stroke is unclear.
Methods
Mice were trained pre-operatively on a skilled reaching task. Following focal ischemic lesions, mice received rehabilitative training either twice daily (high intensity), once daily (low intensity), or not at all (control) to determine the effects of rehabilitative training intensity on skilled motor performance.
Results
Within 7 days, the high intensity trained mice achieved pre-ischemic levels of performance. Mice receiving low intensity training eventually reached similar performance levels but required a greater quantity of training. Training intensity did not consistently affect the maintenance of performance gains, which were partially lost over time in both groups.
Discussion
These data indicate that increased training intensity increases the rate of functional improvements per time and per training session following ischemic insult. Thus, training intensity is an important variable to consider in efforts to optimize rehabilitation efficacy.
Behavioral experience, in the form of skilled limb use, has been found to impact the structure and function of the central nervous system, affecting post-stroke behavioral outcome in both adaptive and maladaptive ways. Learning to rely on the less-affected, or non-paretic, body side is common following stroke in both humans and rodent models. In rats, it has been observed that skilled learning with the non-paretic forelimb following ischemic insult leads to impaired or delayed functional recovery of the paretic limb. Here we used a mouse model of focal motor cortical ischemic injury to examine the effects of non-paretic limb training following unilateral stroke. In addition, we exposed some mice to increased bimanual experience in the home cage following stroke to investigate the impact of coordinated dexterous limb use on the non-paretic limb training effect. Our results confirmed that skilled learning with the non-paretic limb impaired functional recovery following stroke in C56BL/6 mice, as it does in rats. Further, this effect was avoided when the skill learning of the non-paretic limb was coupled with increased dexterous use of both forelimbs in the home cage. These findings further establish the mouse as an appropriate model in which to study the neural mechanisms of recovery following stroke and extend previous findings to suggest that the dexterous coordinated use of the paretic and non-paretic limb can promote functional outcome following injury. Keywords: experience-dependent plasticity, learned nonuse, motor cortex, motor rehabilitation, stroke
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