Restoring After Central Nervous System Injuries: Neural Mechanisms and Translational Applications of Motor Recovery

Abstract

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are leading causes of long-term disability. It is estimated that more than half of the survivors of severe unilateral injury are unable to use the denervated limb. Previous studies have focused on neuroprotective interventions in the affected hemisphere to limit brain lesions and neurorepair measures to promote recovery. However, the ability to increase plasticity in the injured brain is restricted and difficult to improve. Therefore, over several decades, researchers have been prompted to enhance the compensation by the unaffected hemisphere. Animal experiments have revealed that regrowth of ipsilateral descending fibers from the unaffected hemisphere to denervated motor neurons plays a significant role in the restoration of motor function. In addition, several clinical treatments have been designed to restore ipsilateral motor control, including brain stimulation, nerve transfer surgery, and brain–computer interface systems. Here, we comprehensively review the neural mechanisms as well as translational applications of ipsilateral motor control upon rehabilitation after CNS injuries.

Electrical stimulation for therapeutic approach

“…Unfortunately, patients with CNS injury suffer from disruptions of the motor signal transmission and often have permanent disconnections of the motor descending pathway. However, this could be compensated by adoptions of different pathways due to the ability of the neuroplasticity, which occurs naturally after injuries 104–106 . Depending on the location and severity of the lesions, functional and anatomical reorganizations of the neuron circuits compensate for damaged pathways with alternative pathways, which are connected between intact neurons as shown in Figure 4A 104 .…”

“…The corticospinal upper neuron axons from ipsilateral cortex sprout across the midline within the spinal cord for motor function recovery (A6). Reproduced under terms of the CC‐BY license 104 . Copyright 2022, The Authors, published by Springer Nature.…”

“…Reproduced under terms of the CC-BY license. 104 Copyright 2022, The Authors, published by Springer Nature. (B) Electrical stimulation of brain, brainstem, and spinal cord for motor recovery.…”

“…These injuries specifically from external trauma, such as physical accidents and sportrelated accidents, have a devastating impact on voluntary control of the body and other physiological functions, further resulting in a social and economic burden on patients. [99][100][101][102][103][104] Therefore, understanding the recovery mechanism of motor and autonomic functions that regulate the circuits residing in the CNS system is essential.…”

“…However, this could be compensated by adoptions of different pathways due to the ability of the neuroplasticity, which occurs naturally after injuries. [104][105][106] Depending on the location and severity of the lesions, functional and anatomical reorganizations of the neuron circuits compensate for damaged pathways with alternative pathways, which are connected between intact neurons as shown in Figure 4A. 104 With local motor cortex lesions, the network plasticity occurs in perilesional areas to replace the motor functions of injured region (Figure 4A1).…”