Bridging the Gap Between the Peripheral and Central Nervous Systems: Mutual Interactions in Responses to Neuronal Injury

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Background

Injuries to peripheral neurons result in extensive remodeling of the injured area as well as the neural circuits associated with the damaged functions. This is critical to orchestrate the regenerative response and allow reconnection of the axons with their original tissue target. Axons distal to the injury undergo Wallerian degeneration and chromatolysis, neurons transition from a transmitting to a regenerative mode, and glia and immune cells rapidly activate to support axonal regrowth. Moreover, in the central nervous system, adaptive and maladaptive plasticity can occur in response to peripheral injury. These concomitant events impact nerve repair and functional recovery, and are driven by distinct neuronal, glial and immune cell populations found throughout the nervous systems. In order to improve nerve repair, it is beneficial to apply treatments targeting both peripheral and central nervous systems which could modulate the heterogeneous cell response to the injury.

In the nerve injury field, events happening in the peripheral or in the central nervous system have often been approached as distinct despite being interconnected, possibly due to their complex response following injury which involves different glial - Schwann cells versus oligodendrocytes/astrocytes - and immune cell populations - macrophages versus microglia - in the PNS and CNS respectively. However, accumulating evidence suggests that the central nervous system is also an important player in peripheral nerve regeneration. Conversely, peripheral nerve components such as Schwann cells appear to take part of the CNS injury response.

This Research Topic aims to “bridge the gap” between the two by bringing together experts focusing on either field. We aim to provide a comprehensive overview of the cellular reactivity after peripheral nerve injury. We seek Original Research, Review, Mini-Review, Hypothesis and Theory, Perspective, Clinical Trial, Case Report and Opinion articles that cover, but are not limited to, the following topics:

• Molecular mechanisms of neuronal signaling after injury
• The Epigenetics of the nerve injury
• Inflammatory responses in the central and peripheral nervous systems
• Inflammatory responses in the soma of injured neurons, the role of glial and immune cells
• Astrocytes and microglia contribution to pain perception and neuroinflammation
• Interaction between Schwann cells and axons during regeneration
• Interaction between DRGs and satellite glial cells for/ after nerve repair
• Remodeling of neuronal circuits in the spinal cord after nerve injury
• Novel technical approaches to explore cellular reactivity to axonal injury
• Multiple roles of the immune response during PNS regeneration
• Role of CNS and PNS glia at the nerve terminals
• Therapeutic approaches to promote nerve regeneration targeting both peripheral and central nervous systems

Keywords: Nerve Injury, Schwann Cells, DRG, PNS regeneration, Axonal injury, Satellite Glial Cell

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