Introduction: A growing body of literature supports acute changes to skeletal muscle physiology in response to stroke-induced central nervous system injury. While stroke survivors depend on rehabilitation to facilitate functional recovery, study of post-stroke rehabilitation and mechanisms of recovery remains limited. The current work addresses development of a Robot-Assisted Mechanical Therapy (RAMT) device and facilitation of reproducible, objective analysis of post-stroke rehabilitation. We hypothesize that RAMT permits systematic study of post-stroke mechano-physiotherapy and restores hindlimb function after stroke by protecting against skeletal muscle injury.
Methods: Wistar rats (male, N=26) were subjected to middle cerebral artery occlusion (MCAO), after which they received daily RAMT (RAMT+; 0.5N force, 1Hz frequency, 10mm linear motion over medial stroke-affected gastrocnemius) or none (RAMT-; anesthesia only) for 14 days. Assessment of gait, sensorimotor behavior, and muscle perfusion quantified effects of RAMT on post-stroke function, while skeletal muscle analysis (RT-PCR, immunohistochemistry) evaluated expression of myostatin, a molecular target of stroke.
Results: Compared to RAMT- controls, RAMT+ rats benefited from higher perfusion in stroke-affected gastrocnemius (47.7%, p<0.05). RAMT+ improved post-stroke gait and sensorimotor behavior, evidenced by better track width (11.9%, p<0.05), less time in quad support (54.4%, p<0.05), greater travel distance (60.5%, p<0.05), and more time mobile (41.7%, p<0.05). Additionally, RAMT+ protected from post-stroke induction of myostatin, decreasing mRNA and protein expression (39.1% and 88.6% respectively, p<0.05).
Conclusion: RAMT facilitates reproducible, objective, pre-clinical study of post-stroke mechano-physiotherapy. RAMT successfully improves muscle perfusion, rescues gait deficits, preserves sensorimotor behavior, and attenuates the stroke-induced rise in myostatin. Ongoing efforts focus to characterize the mechano-sensitive miRNA transcriptome in skeletal muscle and employ electrophysiology to quantitatively map post-stroke neuroplasticity in response to RAMT.