A Therapeutic Strategy for Lower Motor Neuron Disease and Injury Integrating Neural Stem Cell Transplantation and Functional Electrical Stimulation in a Rat Model

Abstract

Promising treatments for upper motor neuron disease are emerging in which motor function is restored by brain–computer interfaces and functional electrical stimulation. At present, such technologies and procedures are not applicable to lower motor neuron disease. We propose a novel therapeutic strategy for lower motor neuron disease and injury integrating neural stem cell transplantation with our new functional electrical stimulation control system. In a rat sciatic nerve transection model, we transplanted embryonic spinal neural stem cells into the distal stump of the peripheral nerve to reinnervate denervated muscle, and subsequently demonstrated that highly responsive limb movement similar to that of a healthy limb could be attained with a wirelessly powered two-channel neurostimulator that we developed. This unique technology, which can reinnervate and precisely move previously denervated muscles that were unresponsive to electrical stimulation, contributes to improving the condition of patients suffering from intractable diseases of paralysis and traumatic injury.

A Wirelessly Powered 4-Channel Neurostimulator for Reconstructing Walking Trajectory

“…The cuff electrodes we developed previously [ 8 , 21 ] were placed onto the rat’s peroneal nerve and tibial nerve to generate dorsal and plantar flexion of the ankle joint, respectively, and also connected to the branch of the sciatic nerve (connected to femoral biceps) and the femoral nerve to generate knee flexion and extension, respectively. The stimulation signal of nerves was set at 50 Hz to generate tetanic contraction of muscles, and its duration was set at 0.2 ms.…”

“…To conduct control of the rat knee and ankle joint angles using a high-speed camera, the current position of the rat leg has to be detected through the camera. We used the same experimental setup in our previous study [ 8 , 21 ]. A camera (MQ003CG-CM, Ximea, Münster, Germany) was used to detect the angles of the knee and ankle joints using markers on a rat.…”

“…Recovery of muscle activity has been found by FES applied to the peripheral nerves after injection of motor neurons into the sciatic nerve of a rat. Muscle atrophy was prevented by applying a motor neuron injection and FES even if the muscle was denervated [ 7 , 8 ].…”