Objective: To evaluate whether electrical stimulation of the locomotor mesencephalic region (LMR) in rats with lesioned sensorimotor cortex improves (1) locomotion assessed by the CatWalk test and and (2) skilled walking using the ladder rung walking test.

Background: Maladaptive plasticity (e.g. excessive spasticity) may limit functional motor recovery after stroke. Invasive stimulation of the motor cortex has been suggested to counteract maladaptive plasticity in stroke patients. However this approach failed to show any benefit. Since LMR is involved in subcortical gait coordination, this area might be a promising target for invasive stimulation in stroke patients with motor deficits.

Methods: Male Wistar rats were trained to cross the runway of the CatWalk, a video-based analysis system to assess static and dynamic gait parameters. Another group was trained to cross a horizontal ladder consisting of rungs and transparent side walls. Each crossing was recorded by a camera. Paw placement on the rung was rated using a foot fault scoring system. After 7 days of training, photothrombotic lesion was induced in the right sensorimotor cortex and thereafter, a microelectrode was implanted in the LMR ipsilateral to the lesion. Before locomotor testing, stimulation intensity was determined for each animal; the lowest current evoking locomotion was chosen to perform behavioral tests. All tests were performed 48 hours after surgery, first without stimulation and three hours later with high-frequency stimulation (130Hz).

Results: Simultaneously to the onset of LMR-stimulation, a significantly higher walking speed, a shorter single stance of the left forepaw and a shorter stance duration of the left fore-/hindpaw was detected in stimulated animals by the CatWalk system. We found a significantly shorter step cycle duration and duty cycle in stimulated animals. In the ladder rung walking test, stimulated animals revealed a significantly lower foot fault score compared to non-stimulated rats. All effects were no longer seen when stimulation was stopped.

Conclusions: Improvement of locomotion after LMR-stimulation might be due to the activation of unlesioned, alternative motor pathways connected to the LMR. Thus, LMR-stimulation might be an approach to counteract maladaptive effects of a cortical lesion when stimulation is applied continuously over an adequate time.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-of-the-locomotor-mesencephalic-region-in-rats-with-lesioned-sensorimotor-cortex-a-model-of-functional-motor-recovery-after-stroke/