Official websites use. Share sensitive information only on official, secure websites. Ischemic stroke is a leading cause of disability world-wide.
Mounting evidence supports neuromuscular pathology following stroke, yet mechanisms of dysfunction and therapeutic action remain undefined. The objectives of our study were to investigate neuromuscular pathophysiology following ischemic stroke and to evaluate the therapeutic effect of Robot-Assisted Mechanical massage Therapy RAMT on neuromuscular junction NMJ morphology.
Using an ischemic stroke model in male rats, we demonstrated longitudinal losses of muscle contractility and electrophysiological estimates of motor unit number in paretic hindlimb muscles within 21 days of stroke. Histological characterization demonstrated striking pre- and postsynaptic alterations at the NMJ. Stroke prompted enlargement of motor axon terminals, acetylcholine receptor AChR area, and motor endplate size. Paretic muscle AChRs were also more homogenously distributed across motor endplates, exhibiting fewer clusters and less fragmentation.
Most interestingly, NMJs in paretic muscle exhibited increased frequency of polyaxonal innervation. This finding of increased polyaxonal innervation in stroke-affected skeletal muscle suggests that reduction of motor unit number following stroke may be a spurious artifact due to overlapping of motor units rather than losses.
Furthermore, we tested the effects of RAMT β which we recently showed to improve motor function and protect against subacute myokine disturbance β and found significant attenuation of stroke-induced NMJ alterations. RAMT not only normalized the post-stroke presentation of polyaxonal innervation but also mitigated postsynaptic expansion. These findings confirm complex neuromuscular pathophysiology after stroke, provide mechanistic direction for ongoing research, and inform development of future therapeutic strategies.
