Electrophysiological transmission of motor signals during stroke recovery in rats

Abstract

Background – Stroke patients often experience motor function impairments as a result of damaged motor fibres such as the corticospinal tract (CST) and alternate motor fibres (aMFs). However, the relationship and contribution of these tracts in motor function recovery are still incompletely understood. Pre-clinical studies are needed to elucidate the role and relationship of aMFs in stroke recovery. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that can be used as 1) a diagnostic tool to study cortical excitability and integrity of motor tracts or 2) a therapeutic tool to alter cortical excitability. Currently, the effectiveness of repetitive TMS (rTMS) treatment in the clinic shows inconsistent findings on improved cortical activation and motor function. Therefore, further investigation is needed to test the effectiveness of inhibitory versus excitatory rTMS after stroke. Methods – For the first part of this study, twelve adult female Long-Evans rats were given either a sham or a focal CST lesion to study the contribution of the aMFs on the electrophysiological transmission of motor signals. Action potentials were elicited in the motor cortex with TMS and recorded in the forepaw with needle electromyography to determine the lowest motor threshold (MT) that allowed signal transmission pre-stroke and four times post-stroke. In the second part of this study, 21 male Sprague-Dawley rats with a motor cortex lesion, were given nine rTMS sessions over nine days. They received one of three different rTMS interventions (inhibitory, excitatory and sham (n = 7/group)) to study their effect on motor signal transmission and motor function recovery post-stroke. MT was determined pre-treatment and 1 day and 8 days post-treatment. Results – Part I: the animals with a CST lesion showed no increase in MT (60.83 ± 5.27) compared to the animals without lesion (60.00 ± 5.47) in the acute phase post-stroke. However, there was a significant increase of MT in the late sub-acute phase (65.33 ± 4.50). Part II: there was difference in MT and motor function between treatment groups. Conclusions – This study shows that a focal lesion to the CST in the internal capsule does not affect the electrophysiological transmission of motor signals in the acute phase of stroke recovery, whereas it does decrease transmission in the late sub-acute phase. Secondly, this study shows that there is no effect of rTMS treatment on motor signal transmission and motor function in animals with a lesion in the motor cortex. Both these findings lay the groundwork for the improvement of diagnosis and prognosis for personalized therapies of stroke patients to improve their clinical outcome.