Targeting axon guidance cues for neural circuit repair after spinal cord injury

Abstract

At least two-thirds of spinal cord injury cases are anatomically incomplete, without complete spinal cord transection, although the initial injuries cause complete loss of sensory and motor functions. The malleability of neural circuits and networks allows varied extend of functional restoration in some individuals after successful rehabilitative training. However, in most cases, the efficiency and extent are both limited and uncertain, largely due to the many obstacles of repair. The restoration of function after anatomically incomplete injury is in part made possible by the growth of new axons or new axon branches through the spared spinal cord tissue and the new synaptic connections they make, either along the areas they grow through or in the areas they terminate. This review will discuss new progress on the understanding of the role of axon guidance molecules, particularly the Wnt family proteins, in spinal cord injury and how the knowledge and tools of axon guidance can be applied to increase the potential of recovery. These strategies, combined with others, such as neuroprotection and rehabilitation, may bring new promises. The recovery strategies for anatomically incomplete spinal cord injuries are relevant and may be applicable to traumatic brain injury and stroke.

Transcriptomic analysis of ipsilateral spinal cord in rats after bone fracture

“…Axon guidance is the process by which neurons send out axons and form synapses in the correct location. Good axon guidance can enhance the recovery potential after spinal cord injury [37]. The enrichment results of the sphingolipid signaling pathway, axon guidance, and dopaminergic synapses are consistent with the enrichment results of the synaptic-related GO terms.…”

Protein arginine methyltransferase 8 regulates ferroptosis and macrophage polarization in spinal cord injury via glial cell‐derived neurotrophic factor

“…Moreover, clinical trials are needed to translate PRMT8/GDNF‐based precision therapy into clinical practice. Additionally, merely mitigating secondary injury may have limited effects because of the disruption of axons at the time of injury 45 . Therefore, strategies for axon recovery, combined with neuroprotection and anti‐inflammatory approaches, may exert greater effects in the repair of injured spinal cord.…”

Blockage of ERCC6 Alleviates Spinal Cord Injury Through Weakening Apoptosis, Inflammation, Senescence, and Oxidative Stress

“…Spinal cord injury (SCI), a highly disabling neurological disorder, usually leads to permanent motor and sensory dysfunctions, affecting approximately 250,000–500,000 individuals each year ( Zhou et al, 2020 ). SCI is characterized by the lesion cores or fibrotic scars without viable neural tissues, the scars of astrocytes around the lesion cores, and the area of surviving neural tissues with limited functions and functional plasticity ( Zou, 2021 ). Despite the structural support provided by the lesion scars, there is a suppressive environment for the regeneration of severed axons, thereby suppressing the re-debilitation of the original target ( Kuboyama et al, 2021 ).…”