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Repair of the Peripheral Nerve-Remyelination that Works.

Fex Svennigsen A, Dahlin LB - Brain Sci (2013)

Bottom Line: The review starts with a description of the current state of knowledge about the initial events after injury, followed by Wallerian degeneration, and subsequent regeneration.The review concludes by describing the target re-innervation, which today is one of the most serious problems for nerve regeneration.It is clear, compiling this data, that even though regeneration of the peripheral nervous system is possible, more research in this area is needed in order to perfect the outcome.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine-Neurobiology Research, University of Southern Denmark, J.B. Winsløws vej 21.1, Odense DK-5000, Denmark. aasvenningsen@health.sdu.dk.

ABSTRACT
In this review we summarize the events known to occur after an injury in the peripheral nervous system. We have focused on the Schwann cells, as they are the most important cells for the repair process and facilitate axonal outgrowth. The environment created by this cell type is essential for the outcome of the repair process. The review starts with a description of the current state of knowledge about the initial events after injury, followed by Wallerian degeneration, and subsequent regeneration. The importance of surgical repair, carried out as soon as possible to increase the chances of a good outcome, is emphasized throughout the review. The review concludes by describing the target re-innervation, which today is one of the most serious problems for nerve regeneration. It is clear, compiling this data, that even though regeneration of the peripheral nervous system is possible, more research in this area is needed in order to perfect the outcome.

No MeSH data available.


Related in: MedlinePlus

Timeline of major events important for nerve repair after injury, depicting many of the events known (that could be found in the literature) to occur after an injury. Most of these are likely important for the repair process.
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brainsci-03-01182-f001: Timeline of major events important for nerve repair after injury, depicting many of the events known (that could be found in the literature) to occur after an injury. Most of these are likely important for the repair process.

Mentions: The increase of calcium in turn activates intracellular cascades and gene regulatory proteins, such as mitogen-activated protein kinase family (MAPK), extracellular signal-regulated protein kinases (ERKs) and c-jun N-terminal protein kinases (JNKs) [22]. ERK 1/2 is activated already at 20 min post injury, while an activation of P38 MAPK appears six hours later (Figure 1). The activation of P38 MAPK, one of several molecules important for the progression of Wallerian degeneration, occurs subsequent to the increases in the levels of calcium, neuregulin, and Fibroblast Growth Factor-2 (FGF-2). This activation induces demyelination [23,24,25,26]. Further, down-stream in this signal cascade is the transcription factor c-jun, which is a global regulator of the Schwann cell injury response. The activation of c-jun is essential for the gene expression, for the function of the denervated Schwann cells and the formation of bands of Büngner and for Schwann cell proliferation and myelin clearance after injury in the distal segment (Figure 1) [11,27,28,29]. Without c-jun activation in Schwann cells, both unmyelinated and myelinated dorsal root ganglia (DRG) neurons are twice to three times as likely to die following axonal damage [29,30]. The absence of c-jun activation in Schwann cells also impairs axonal regeneration and results in a loss of the necessary increased expression of several neurotrophic factors that occur when c-jun is present [30]. The rapid activation of ERK 1/2 is a prerequisite for Schwann cell proliferation and the presence of ERK 1/2, as well as other transcription factors, like ATF 3, is important for axonal outgrowth [22]. These findings are particularly relevant since Schwann cell apoptosis increases significantly if nerve repair is delayed [31]. Even though these investigations are made in rodents, it likely applies to all mammals. It also underlines the importance of early repair after nerve injury in humans [9,11].


Repair of the Peripheral Nerve-Remyelination that Works.

Fex Svennigsen A, Dahlin LB - Brain Sci (2013)

Timeline of major events important for nerve repair after injury, depicting many of the events known (that could be found in the literature) to occur after an injury. Most of these are likely important for the repair process.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061866&req=5

brainsci-03-01182-f001: Timeline of major events important for nerve repair after injury, depicting many of the events known (that could be found in the literature) to occur after an injury. Most of these are likely important for the repair process.
Mentions: The increase of calcium in turn activates intracellular cascades and gene regulatory proteins, such as mitogen-activated protein kinase family (MAPK), extracellular signal-regulated protein kinases (ERKs) and c-jun N-terminal protein kinases (JNKs) [22]. ERK 1/2 is activated already at 20 min post injury, while an activation of P38 MAPK appears six hours later (Figure 1). The activation of P38 MAPK, one of several molecules important for the progression of Wallerian degeneration, occurs subsequent to the increases in the levels of calcium, neuregulin, and Fibroblast Growth Factor-2 (FGF-2). This activation induces demyelination [23,24,25,26]. Further, down-stream in this signal cascade is the transcription factor c-jun, which is a global regulator of the Schwann cell injury response. The activation of c-jun is essential for the gene expression, for the function of the denervated Schwann cells and the formation of bands of Büngner and for Schwann cell proliferation and myelin clearance after injury in the distal segment (Figure 1) [11,27,28,29]. Without c-jun activation in Schwann cells, both unmyelinated and myelinated dorsal root ganglia (DRG) neurons are twice to three times as likely to die following axonal damage [29,30]. The absence of c-jun activation in Schwann cells also impairs axonal regeneration and results in a loss of the necessary increased expression of several neurotrophic factors that occur when c-jun is present [30]. The rapid activation of ERK 1/2 is a prerequisite for Schwann cell proliferation and the presence of ERK 1/2, as well as other transcription factors, like ATF 3, is important for axonal outgrowth [22]. These findings are particularly relevant since Schwann cell apoptosis increases significantly if nerve repair is delayed [31]. Even though these investigations are made in rodents, it likely applies to all mammals. It also underlines the importance of early repair after nerve injury in humans [9,11].

Bottom Line: The review starts with a description of the current state of knowledge about the initial events after injury, followed by Wallerian degeneration, and subsequent regeneration.The review concludes by describing the target re-innervation, which today is one of the most serious problems for nerve regeneration.It is clear, compiling this data, that even though regeneration of the peripheral nervous system is possible, more research in this area is needed in order to perfect the outcome.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine-Neurobiology Research, University of Southern Denmark, J.B. Winsløws vej 21.1, Odense DK-5000, Denmark. aasvenningsen@health.sdu.dk.

ABSTRACT
In this review we summarize the events known to occur after an injury in the peripheral nervous system. We have focused on the Schwann cells, as they are the most important cells for the repair process and facilitate axonal outgrowth. The environment created by this cell type is essential for the outcome of the repair process. The review starts with a description of the current state of knowledge about the initial events after injury, followed by Wallerian degeneration, and subsequent regeneration. The importance of surgical repair, carried out as soon as possible to increase the chances of a good outcome, is emphasized throughout the review. The review concludes by describing the target re-innervation, which today is one of the most serious problems for nerve regeneration. It is clear, compiling this data, that even though regeneration of the peripheral nervous system is possible, more research in this area is needed in order to perfect the outcome.

No MeSH data available.


Related in: MedlinePlus