Effect of forced arm use and voluntary exercise on functional motor recovery and gene expression profiles after focal ischaemia

Background and purpose: Both the immobilization of the unaffected arm combined with physical therapy (forced arm use, FAU) and voluntary exercise (VE) as model for enriched environment are promising approaches to enhance recovery after stroke. The genomic mechanisms involved in long-term plasticity changes after different means of rehabilitative training post-stroke are largely unexplored. The present investigation explored the effects of these physical therapies on behavioral recovery and molecular markers of regeneration after experimental ischaemia.

Methods: 42 Wistar rats were randomly treated with either FAU (1-sleeve plaster cast onto unaffected limb at 8/10 days), VE (connection of a freely accessible running wheel to cage), or a cage control condition for 10 days starting at 48 hours after photothrombotic stroke of sensory-motor cortex. Functional outcome was measured using a battery of sensory-motor tests at baseline before ischaemia, after ischaemia, after the training period of 10 days, and at 3 and 4 weeks after ischaemia by an investigator blinded to the experimental groups. For gene expression changes samples were taken from the ipsi- and contralateral cortex and the hippocampus. The complete available rat Genome chip was used (GeneChip® Rat Genome 230 2.0 Array), encompassing all known genes and expressed sequence tags for the rat.

Results: Therapy after focal cerebral ischaemia with both FAU and VE compared to cage control condition significantly improved functional recovery after focal ischaemia. The enhancement of functional outcome was retained over 4 weeks after ischaemia. Furthermore, FAU-treated animals had significant better functional recovery compared to the VE-treated group.

Conclusion: Our data demonstrate that physical training modeled by FAU and VE treatment for 10 days initiated 48 hours after photothrombotic stroke significantly and permanently improve functional recovery after stroke. Furthermore, we suggest that FAU is superior to voluntary physical activity after small ischaemia. Although human studies indicate that FAU after stroke improves functional recovery, experimental studies are more controversial. Here we can substantiate the positive effect of FAU on functional recovery after small ischaemia. Conclusively, our data highlight the degree of transcriptional changes after different means of rehabilitative training post-stroke, and provide insight into functional pathways of relevance for recovery mechanisms in neural networks.