Schwann Cells and Nerve Regeneration

Schwann Cells and Nerve RegenerationYinghui Xu AbstractThe studyity of the nervous system cellular phones atomic quash 18 glial cells, which pay various properties and moves. Schwann cells argon the principal glial cells of the off-base nervous system(PNS). In normal steels, they function to form insulating myelin sheath around axons and provide support to neurons. In injured fondnesss, however, they change their properties and switch function to that of supporting spunk innovation. taste their cap mightiness in the switching process could lead to better manipulation for those suffering from kernel injuries. This essay gives an overview of the structure and breeding of Schwann cells and the causes of facial have a bun in the ovenion injuries. It as well as provides an explanation in the role that Schwann cells play in supporting establishment vicissitude and how unalike approach could press face positive feedback.Introduction to Schwann cellsSchwann cells a tomic number 18 the virtually abundant glial cells in the PNS. They atomic number 18 a respective(a) sort out of cells originated from flighty crest cells and they play an essential role in the PNS of both vertebrate and invertebrate. They can be subdivided by their morphology and anatomical reference location into four subsets, that is to say the myelinating Schwann cells, non-myelinating Schwann cells, satellite cells and perisynaptic Schwann cells (Armati Mathey, 2014).These different types of Schwann cells and their anatomical locations atomic number 18 shown in Figure 1.Figure 1 Locations of different types of Schwann cells in the PNS(Armati Mathey, 2007). (a) transmit Schwann cells in the dorsal root ganglia. (b) Non myelinating Schwann cells in mixed peripheral device nerve fibres. (c) Myelinating Schwann cells in mixed nerve fibres. (d)Perisynapic Schwann cells at the neuromuscular junction (NMJ). separately subset of Schwann cells has different functions. For exa mple, perisynaptic Schwann cells are essential for modulating NMJ function whereas satellite Schwann cells adopt the ability to regulate the neuronal environment (Armati Mathey, 2007). Non-myelinating Schwann cells associate with several axons via a private layer of myelin.Myelinating Schwann cells are the most studied Schwann cell subset and they are most known for their function in speeding up the propagation of attain potentials. Myelinating Schwann cells wrap around axons of neurons to form the insulating myelin sheath. Between the myelin sheaths are periodic gaps called nodes of Ranvier where action potentials occur. Action potentials jump from one node to the coterminous node,in a process called saltatory conduction, which increases conduction velocity and get outs signals to be propagated long distances without any(prenominal) degradation.In addition to their function in the propagation of action potentials, Schwann cells have many subtle yet essential functions, one o f which is its role in nerve regeneration. This essay will focus on the characteristics of Schwann cells and how they answer to hurt that allows the PNS to regenerate after damage.Development of Schwann cellsThe myelinating and nonmyelinating Schwann cells in the PNS are originated from the neural crest, which is a multipotent structure that also gives rise to new(prenominal) glial cells of the PNS. Schwann cell development occurs in well-defined developmental steps, which are strictly modulate by a number of signals. (Figure 1.2). During the first stage of Schwann cell development, neural crest cells produces Schwann cell precursors. These then generate the callow Schwann cells. At birth, the immature Schwann cells differentiate into either the myelinating or nonmyelinating Schwann cells.Figure 1.2 Main stages of Schwann cell development (Jessen, et al., 2015).Peripheral nerve blurPeripheral nerve disfigurement is injury to peripheral nervous thread. It can occur at any exp ress along a peripheral nerve. Nerves can be change by a number of mechanisms such as compression, traction, or a quash. They can also get damaged by toxins, infection and personal agents such as freezing and electrical current (Murray, 2014).2.1 Structure of peripheral nervesIn order to understand the pathophysiology of peripheral nerve injury, it is heavy to know the anatomical structure of a peripheral nerve (Figure 2). axon is made up of neurofilaments and microtubules that transport substances between the nerve cell consistency and the axon terminal. All peripheral nerve axons are associated with Schwann cells. In larger (myelinated) nerves, Schwann cells generate layers of myelin around the axon to form a sheath, whereas in lesseneder (unmyelinated) nerves a single Schwann cell associates with several axons via a single layer of myelin. The joining tissue (the endoneurium) that surrounds the axon-Schwann cell unit provides structural support to individual axons. Nerve fibres are further protected by a touch multipayered cellular tube (the perineurium) that surround nerve fascicles (Jessen, et al., 2015 Murray, 2014). Finally, the constitutional nerve trunks are protected by the outermost connective tissue (the epineurium) (Murray, 2014).Figure 2 Anatomical structure and main cellular components of a peripheral nerve (Jessen, et al., 2015).2.2 Pathogenesis of peripheral nerve injury disregarding of cause, there is a limited range of responses to peripheral nerve injury. Wallerian reversion. Wallerian degeneration occurs when there is a loss of axonal continuity by cut or crush. Communication is lost between the cell body and the surgical incision of nerve distal to the site of injury. As a consequence, the distal nerve segment degenerate. The details of the initiation of this degeneration remain to be in full explained, exactly evidence shows that an increase in intraaxonal calcium activates proteases, which leads to the degradation of the axon cytoskeleton.Wallerian degeneration is also associated with the degeneration of the myelin sheath by lipases and proteases. Schwan cells (and posterior macrophages) are involved in further myelin degeneration. Schwann cells also grow and undergo morphological changes and are induced to generate molecules that will be required for nerve regeneration later on.Figure 2.2 Wallerian degeneration2.3 Types of peripheral nerve injuryThere are devil main types of peripheral nerve injury (Burnett Zager, 2004). The first type is axonotmesis, in which axons are damaged further the connective tissue sheaths are preserved. This type of injury can be caused by compression, traction and laceration but it is mainly seen in crush injury (Murray, 2014). Axonal regeneration is very effective and function is restored in 3-4 hebdomad when modelled in rodents by nerve crush (Jessen, et al., 2015). The second and the more spartan type of nerve injury, neurotmesis, involves damage to both the ax on and connective tissue sheath. Severe traction, crush and laceration can lead to neurotmesis (Murray, 2014). In this case, functional convalescence is generally poor.The Schwann cell injury responseWhen nerve injury occurs, Schwann cells respond rapidly and undergoes a radical phenotypical change. The process has two major parts, one of which is the reversal of myelin differentiation. Molecules involved in forming Schwann cells before myelination are up-regulated slice myelin associated genes are down-regulated (Jessen, et al., 2015). The other part of the response involves the expression of phenotypes that are not associated with normal Schwann cells or immature Schwann cells. These cells have a better supportive phenotype and tot up to the nerve regeneration process.Schwann cells function in multiple modes during nerve regeneration. There are four main functions that Schwann cells bring out in response to nerve injury (Niu, 2009). These functions include(1) activating macr ophages and elucidation debris (2) forming the Bungner band (3) secreting neurotropic grammatical constituents (4) secreting ECM and CAM.3.1 Schwann cells put out cytokines to attract macrophagesWhen an axon is cut, the end still attached to the cell body is called the proximal segment, while the other end is called the distal segment. The process of nerve regeneration involves the defining of axonal sprouts at the proximal stump and the growing of axonal sprouts until they see the distal stump. Efficient nerve regeneration needs a satisfactory microenvironment which is regulated by macrophages via their phagocytotic and pass offing functions (Barrette, et al., 2008).Experiment by Huang et al. showed that Schwann cells can suppress macrophage migration inhibitory factor (MIF) when peripheral nerve injury occurs (Huang, et al., 2002). MIF is a pluripotent cytokine that functions in inflammatory reactions and immune responses. It also plays an important role in macrophage act ivation, attracting macrophages to clear away debris at the injury site and regulate the microenvironment to allow for efficient regeneration.Nishio et al. administered anti-MIF polyclonal antibody into regenerating rat sciatic nerves using the silicone chamber model. The results showed that the regeneration length of the nerve in the anti-MIF antibody-treated group was importantly shorter than that in the control group at weeks 2,4,6 after surgery (Nishio, et al., 2002). In addition, a large number of apoptotic Schwann cells were observed the anti-MIF antibody-treated nerves. These results suggest that MIF also contributes to the speedup of peripheral nerve regeneration and the prevention of Schwann cell apoptosis (Nishio, et al., 2002). in like manner MIF, other cytokines such as MCP-1 were also secreted by Schwann cellsWhen peripheral nerve injury occurs, Schwann cells secrete MIF and other cytokines which activates macrophages. Invading macrophages also secrete cytokines which c ontribute to Schwann cell proliferation (Kubota Suzuki, 2000). Injury-induced Schwann cell proliferation plays an important role in axon regeneration as described in the following section. Schwann cells are also up to(p) of phagocytosing myelin and they cooperate with macrophages to clear away myelin and debris (Jessen, et al., 2015), providing a good microenvironment for nerve regeneration to occur.3.2 Schwann cells proliferate to form the Bungner band to choose axonal growthSchwann cells are highly plastic. The change has been characterised as de-differentiation (Chen, et al., 2007), but it is also seen by some groups as activation (Armstrong, et al., 2007). The two call seem to be contradictory to each other, but this can have a simple explanation, which is that the change in Schwann cell phenotypes during Wallerian degeneration in fact involves both of these processes. The conversion ofSchwann cells to meliorate Schwann cells involves both a loss- dedifferentiation and a ga in-activation of phenotypesIn the distal stump of injured nerves, denervated Schwann cells undergo a phenotypic change to form repair Schwann cells. These repair Schwann cells form Bungner bands which are regeneration tracks that provide support for injured nerves and guide regenerating axons to their targets.3.3 Schwann cells secrete neurotropic factors (NTF) to enhance nerve regenerationNTFs are peptides or grim proteins that support the growth and differentiation of neurons. The take aim of their expression is elevated in Schwann cells during nerve injury. Because of their strong function in promoting neuronal growth, they may be used to prevent the impairment of function or death of neurons during nerve injury (Niu, 2009). Most NTFs produce their effects by signalling through receptor tyrosine kinases (Malenka, et al., 2009). NTFs can be divided by their cellular mechanisms into three families, namely the neurotrophin family, the CNTF family and GDNF family (Henderson, 1996)3 .3.1 Neurotrophin familyThe neurotrophin family includes nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3/4/5/6/7 (NT-3/4/5/6/7). There are two receptor types for neurotrophins. The first type is called the tropomyosin receptor kinanse (Trk) which has an high chemical attraction to different neurotrophins. TrkA is the receptor for NGF, Trk B can be the receptor for BGNF, NT-4 and NT-3, and TrkC is activated exclusively by NT-3. The other type of is called p75 neurotrophin receptor which has a low affinity and can bind with all neurotrophins (Niu, 2009)..NGF is the first discovered neurotrophin. It is deprecative for the proliferation and survival of neurons, especially after nerve injury. Schwann cells express an elevated level of NGF during nerve injury, which promotes axonal regeneration and hies the process of nerve repair (Niu, 2009). Recombinant NGF have been produced in laboratory and it is regarded as a practicable therapy for neurode generation of the CNS and PNS (Colangelo, et al., 2005).BDNF help to support the survival of existing neurons and promote the growth and differentiation of new neurons (Huang Reichardt, 2001). Schwann cells that are genetically modified to overly express BDNF significantly improve the survival of spinal gangalion neuron (Pettingil, et al., 2008). Takano et al. developed an in vitro model for retinal explants and showed that BDNF greatly promoted the regeneration of neurites from retinal ganglion cells in a damaged retina. A considerabe number of neurites were observed within 24 time of day in the group containing BDNF while only a small number of neurites were observed after 3 days in the control group (Takano, et al., 2002).Other neutrophins use different ways to accelerate nerve repair when damage occurs. Using NT-3 alone or in combination with other NTFs can promote nerve regeneration in the injured spinal cord (Taylor, et al., 2006 Arvanian, et al., 2006). Research by English et al. showed that neutotrophin-4/5 is required for the archaeozoic growth of regenerating axons in peripheral nerves (English, et al., 2005).3.3.2 Ciliary neurotrophic factor (CNTF) familyThe CNTF family includes CNTF, leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). LIF and IL-6 can act directly on neurons to promote axonal regeneration (Jessen, et al., 2015). The most prominent function of the CNTF family is its prevention of ram neuron degeneration, which suggests that it can be used as a cure treatment for human degenerative repulse neuron diseases (Sendtner, et al., 1992).3.3.3 GDNF familyGDNF is a small protein that supports the survival of many types of neurons including motorneutrons. It can also prevent apoptosis of motor neurons caused by axotomy.3.4 Schwann cells produce extracellular matrix proteins (ECM) and cell adhesion molecules (CAM)The endoneurium surrounding peripheral axons contain a large amount of ECM secreted by Schwann cells. ECM is rich in co llagen and contains glycoproteins such as fibronectin and laminin (Niu, 2009). ECM regulates samara aspects of Schwann cell development including the formation and function of myelin (Court, et al., 2006). In addition, they middle Schwann cell proliferation and axon growth (Armstrong, et al., 2007 Webber Zochodne, 2010).CAMs secreted by Schwann cells are involved in peripheral nerve repair. They play an important role in axon growth and formation of nerve bundles. Study from Lavdas et al showed that Schwann cells have the ability to migrate in the CNS, promoting myelin regeneration and making it possible for remyelination in the CNS (Lavdas, et al., 2006) .Experiment from Park et al. showed that the attachment and proliferation of Schwann cells are affected by special CAMs. It is therefore important to consider choosing optimal CAMs for tissue-engineered nerve regeneration (Park, et al., 2008).SummarySchwann cells use the above four ways to function during peripheral nerve repair. Many years of research have already proved that Schwann cells can secrete a large amount of molecules to support neurons and accelerate the damage repair process. However, further research is needed to show whether AsAlthough the PNS is able to regenerate, much research still needs to done to exploit regeneration potential.