Introduction: Peripheral nerve injury is a critical disorder that can result in the multimode motor and sensory disturbances. The goal of this studywas to review systematically the literature on the role of growth factors in preventing the Schwann cell impairment in surgical peripheral nerve repair.
Method: In this systematic literature review, the role of different vascular endothelial growth factorswere examined in their relations in preventing the Schwann cell impairment in surgical peripheral nerve repair. The authorsused the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to search for articles from databases, select the most relevant articles based on the keywords and conducts a systematic review of the literature.
Discussion: Among the Vascular Endothelial Growth Factors-A, B, C, and D, the authors found that VEGF-B can stimulate nerve regeneration and enhances the general recovery of the tissues' sensation and promote the ability of the innervated tissues to heal. The physiologic relevance of the VEGF indicates that nerve injury induces the endogenous expression the VEGF-B more than the other growth factors because VEGF-B can induce a stronger elongation and branding of neurons and activate complex intra-cellular signaling.
Conclusion: Axons damaged during surgical operations regenerate into the Schwann cell graft when they are in contact with the Schwann cells, but they exhibit no changes when they are in the Schwann cell-eliminated graft. The axons that contacted the astrocytes found in the nerve segments regenerated faster. The lacking ofVEGF-B tend to have impaired nerve regeneration while the nerve injury only increased the endogenous expression of VEGF-B.
Keywords: VEGF-A, B, C, D,growth factors, Schwann cell impairment, surgical peripheral nerve repair.
Peripheral nerve injuries are among the most common upper limb trauma. Peripheral nerve injuries might be the prevalence of injuries of the peripheral nerves are becoming common and debilitating with other 2.8% of trauma patients reported having developed life-threatening peripheral nerve injuries (5). Peripheral nerve injury might lead to bad and long-term functional incapacities. Severe injury in to the motor or sensory organ is the major consequence that is relatedto the type of grievance and usually leads to severe functional shortfalls.
A nerve injury affects the capability of the brain to communicate effectively with muscles and other organs. Injuries can be caused by overstretching or pressing the limb muscles, moreover, other health conditions might result to peripheral neuropathy such as diabetes. Houschyar et al. (1). Approximately eleven thousand Americans are affected by paralysis every year while over 50,000 peripheral nerve repairs procured were performed every year between 1997 and 2002. However, 82% of the cases required end-to-end neuropathy. 18 % of the cases required nerve reconstruction by grafting or tubulization. Most of the cases received nerve autograft, as it is the gold standard for these nerve type injuries, Burnett &Zager, 2004 (52). Peripheral nerve injuries can result in extreme dysfunction especially in the hands. Adequate treatment should be availed to the repair the peripheral nerves as this would also help in preventing the permanent dysfunctions. Crawford & Ferrara (2) Nerve pathology and physiology research have demonstrated that surgical repairs through reconstruction are the most viable. Deumens, Bozkurt, et al, (3) also reported that both end-to-end anastomosis and nerve graft insertion both had shown a significant success. It is essential to get medical attention as soon as possible in the case of a peripheral nerve injurybecause they might be repaired and early treatment might avertproblems from long-lasting injury. Severe peripheral nerve injuries can result to loss of sense in the injured area.
The sort of possibilities depending on the level of severity and consequences after peripheral nerve injury is wide and heavily relies on the type of injury, Kolar&Kingham, 2014 (53). The degree of recovery varies between total distractions of axons with the adjacent layers and recovering levels in neuropraxiaregarding mild crush injuries that affect the sheath thus preserving the reliability and continuity of the connectivity tissues. Peripheral nerve injury is accompanied by responses from the axon segments, proximal and from the neighboring neural cells. The Schwann cells play a vital role in the repair of the nerve, not only regarding the degeneration remyelination but also supporting the growth of axonal, Lopez-Cebral, Silva-Correia, Reis, Silva & Oliveira, 2017 (54).
In surgical peripheral nerve repair, which growth factors can prevent the Schwann cells impairment?This study will systematically review literature for evidence on the most important vascular endothelial growth factor (VEGF) in preventing Schwann cell impairment following surgical peripheral nerve repair.
Fink et al (4) reported that it is also important to note that the nerve injuries are classified into neuropraxia, axonotmesis, and neurotmesis. Neuropraxia is the injury to the myelin sheath only where the axonal sheath because of compression or stretching, which results to the temporary loss of sensory function because of the obstruction of nerve conduction. Gaumann et al, (44) reported that in neuropraxia, the axonal sheath is usually preserved and there is not Wallerian degeneration, but recovery can be complete within days and full recovery within 6 to 8 weeks. Neuropraxiaresults to the diminishing in the ability to perform advanced coordinated actions without muscular impairment. According to Gigo-Benito, Geuna, &Rochkind, (5), axonotmesis refers to the injury that involves the axon and Wallerian degeneration, and the degeneration is distal to the injury site. It is often because of severe crush than the neurapraxia involving the peripheral nerves. They argue that the axons are damaged but then the endoneurium and perineurium remain undamaged. On the other hand, Griffin, Hogan, Chhabra, & Deal (6) reported that the axonotmesis involves only the axon while type 3 injuries involve the disruption of the endoneurium and the perineurium. They also argued that the type four injuries might need surgical intervention with an additional 10-week rest, Lin,Lue, Sanford, Wang &Xin, 2015 (55).Neurotmesis refers to the neuronal continuity because it is a severe type of injury involving the disruption of the nerves. In this injury, the epineurium transacted, and surgical intervention preferred.The first-degree injury is neurapraxia, which also referred as stretch injury involving a temporary conduction blockage that occurs through a section of a nerve with conservation of axon continuity, Ronchi et al., 2017 (7). The frequent cause of Neurapraxia is by a crush injury to the nerve whereby conduction clogged because of the myelin injury. This result to a focal conduction block that lacks Wallerian degeneration because the axon maintains its intact with recovery commonly evident in 3-6 weeks after restoration of myelin continuity. Second-degree injury is the stage where axonotmesis resulting from a severe trauma that causes disintegration of wallerian distal to the stage of injury and proximate axon degeneration to thesubsequent swelling of Ranvier. It defines axonal injury inside a complete endoneurial tube that allows re-growth in the tube, Thomson et al., 2017 (29).Third degree injury describes neurotmesis with the maximum severe level of peripheral nerve injury. This occurs when endoneurial tubes, axon, components of collective tissues and myelin are injured regardless of the conservation of the perineurium, Tezcan, 2017 (47). In the fourth- injury, epineurium is intact while fascicular and endoneurial damaging occurs. Nerve fasciculi are injured but there is preservation of nerve sheath continuity. The fifth degree is the neurotmesis, which involves a total physiological disruption of the whole nerve trunk.
Table 1: nerve injury classification according to the severity
The main goals of surgical peripheral nerve repair are restored function to the impaired nerves. The Schwann cells provide the trophic support by releasing neutrophils like the nerve growth factors, Svennigsen&Dahlin, 2013 (56), Jonsson et al., 2013(57). Schwann cells are the neurilemma cells of the peripheral nervous systems responsible for producing the myelin sheath covering the neuronal axons (Sl, & Keating, 19; Gu, Ding, Yang, & Liu, (9). Guayaquil et al. (10) proposed that VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions. On the other hand, Hanrahan et al. (11) argued that the angiogenic switch for vascular endothelial growth factor VEGF-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression demonstrated that VEGF-B played an important role in cell regeneration.
According to Storkebaum&Carmeliet (26) and Margiana&Aman RA(29), the regenerative capacity of the peripheral nervous systems tends to decline with some factors and the most common factor in the regenerative capacity decline is the age. Observations made show that the level of efficiency of regeneration in the peripheral nervous system reduces later in life.Research conducted in animals, though it may vary sometimes, it indicates a decline with age that can be associated with the decline in the transportation in axon. At the end of motor nerve terminals, it reduces its ability to produce ultra-terminal growth inferior to limited denervation, but to an extent of eliminating terminal sprout, Scott & Ramer, 2009 (58). The levels of the frequency and precision of replacement of the positions of the terminals of the motor nerve are significantly impaired. Ji, 2006 stated that the nerve transection is probably able to result in damage of parent neurons resulting from the nerve transection regarding the age of the animal. The chromatolysis is much stronger and takes longer in older animals to return to its normal state with a lower degree of retrograde axonal atrophy.
For example, according to a study done by Painter et al. (14) involving 24-month-old mice, the impairment of functional recovery a following a nerve injury was slow compared to the functional recovery of the two-month-old animals. Li et al. (27) argued that while there is no intrinsic growth capacity between the old and young sensory neurons in vitro, there was no intrinsic growth capacity in their ability of the two groups to activate growth activated transcriptional programs following the injury. Madura, & Gander, (20) also found that Schwann cell delivery of neurotropic factors for peripheral nerve regeneration is dependent on the VEGF secretion.
Madura, & Gander, (20) nevertheless reported that the age of the nerve graft determines the extent of functional recovery as opposed to th...
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