Abstract
Spinal cord injury (SCI) is a devastating lesion to the spinal cord, which determines the interruption of ascending/descending axonal tracts, the loss of supraspinal control of sensory-motor functions below the injured site, and severe autonomic dysfunctions, dramatically impacting the quality of life of the patients. After the acute inflammatory phase, the progressive formation of the astrocytic glial scar characterizes the acute-chronic phase: such scar represents one of the main obstacles to the axonal regeneration that, as known, is very limited in the central nervous system (CNS). Unfortunately, a cure for SCI is still lacking: the current clinical approaches are mainly based on early vertebral column stabilization, anti-inflammatory drug administration, and rehabilitation programs. However, new experimental therapeutic strategies are under investigation, one of which is to stimulate axonal regrowth and bypass the glial scar. One major issue in axonal regrowth consists of the different genetic programs, which characterize axonal development and maturation. Here, we will review the main hurdles that in adulthood limit axonal regeneration after SCI, describing the key genes, transcription factors, and miRNAs involved in these processes (seen their reciprocal influencing action), with particular attention to corticospinal motor neurons located in the sensory-motor cortex and subjected to axotomy in case of SCI. We will highlight the functional complexity of the neural regeneration programs. We will also discuss if specific axon growth programs, that undergo a physiological downregulation during CNS development, could be reactivated after a spinal cord trauma to sustain regrowth, representing a new potential therapeutic approach.
Highlights
Worldwide, every year up to 500,000 people experience a spinal cord injury (SCI), which usually causes remarkable dysfunctions and disabilities, determining long-lasting and irreversible motor, sensory, and/or autonomic deficits (World Health Organization, 2013)
Motor disabilities following SCI are essentially due to axotomy affecting corticospinal motor neurons (CSMNs), whose cell body is located in the layer V of the motor and somatosensory cortical areas (Figure 1)
Remarkable progress has been made to understand the mechanisms involved in the CSMN axonal degeneration and “tentative” regeneration after SCI
Summary
Every year up to 500,000 people experience a spinal cord injury (SCI), which usually causes remarkable dysfunctions and disabilities, determining long-lasting and irreversible motor, sensory, and/or autonomic deficits (World Health Organization, 2013). This tragic condition determines remarkable economic and social consequences (Thuret et al, 2006). The primary phase involves the initial mechanical injury (compression, distraction, laceration, or transection of the spinal cord): it initiates a cascade of cellular and molecular escalating events, leading to the secondary injury phase. The first hours (immediate stage) are characterized by massive death of neurons and glia, axonal damage, spinal cord swelling, hemorrhage, and ischemia
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