Abstract:

Spinal cord injury (SCI) leads to permanent disability with motor and sensory dysfunctions. The mature mammalian central nervous system (CNS) possesses a limited capacity to regenerate/regrow after injury. Research works on functional restoration from SCI via enhanced sprouting of injured/spared fibers based on molecular mechanisms have greatly increased in recent years, especially using small animal models such as anamniotes and rodents. These results allow us to understand the advanced mechanisms of axonal remodeling after SCI. However,for a successful translation of the mechanisms into human patients with SCI, we have to consider certain anatomical and physiological differences in neural circuits between small animals and humans. For example, the corticospinal tract (CST)has been focused as a therapeutic target to enhance motor functions after SCI. The CST fibers originating from the motor cortex directly connect with spinal interneurons and/or motoneurons, to transmit motor commands to them for achieving voluntary movement. Less dexterous animals such as rodents and cats do not physiologically have a direct connectivity of the CST fibers with spinal motoneurons. Thus, it is generally considered that the CST closely relates to the development of manual dexterity through evolution.Recently, at least part of the CST fibers originating from the contralesional primary motor cortex (MI) in a primate SCI model have been reported to extend into the spinal medial gray matter and the motoneuron pool in conjunction with spontaneous recovery from impaired manual dexterity. The relative number of sprouting CST fibers increased in the motoneuron pool as compared to a normal control. However, such an event is not observed in a rodent SCI model. This indicates that the reorganization pattern of CST fibers below the lesioned site in primates differs from that in rodents.To promote axonal sprouting and regrowth as the strategy for functional recovery in human patients with SCI, the CST fibers are needed to extend over a long distance beyond the lesioned site and connect properly with target spinal neurons. For considering such a therapeutic strategy for human patients, it is essential to understand the mechanisms underlying neural network remodeling to achieve functional recovery in primate animals who are characterized by manual dexterity using precision grip.