scholarly journals A Review on the Role of Endogenous Neurotrophins and Schwann Cells in Axonal Regeneration

2021 ◽  
Author(s):  
Samyak Pandey ◽  
Jayesh Mudgal
Keyword(s):  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Treatment Option ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Pharmacological Intervention ◽  
Post Injury ◽  
Diverse Range ◽  
Physical Trauma

AbstractInjury to the peripheral nerve is traditionally referred to acquired nerve injury as they are the result of physical trauma due to laceration, stretch, crush and compression of nerves. However, peripheral nerve injury may not be completely limited to acquired physical trauma. Peripheral nerve injury equally implies clinical conditions like Guillain-Barré syndrome (GBS), Carpal tunnel syndrome, rheumatoid arthritis and diabetes. Physical trauma is commonly mono-neuropathic as it engages a single nerve and produces focal damage, while in the context of pathological conditions the damage is divergent involving a group of the nerve causing polyneuropathy. Damage to the peripheral nerve can cause a diverse range of manifestations from sensory impairment to loss of function with unpredictable recovery patterns. Presently no treatment option provides complete or functional recovery in nerve injury, as nerve cells are highly differentiated and inert to regeneration. However, the regenerative phenotypes in Schwann cells get expressed when a signalling cascade is triggered by neurotrophins. Neurotrophins are one of the promising biomolecules that are released naturally post-injury with the potential to exhibit better functional recovery. Pharmacological intervention modulating the expression of these neurotrophins such as brain-derived neurotrophic factor (BDNF) and pituitary adenylyl cyclase-activating peptide (PACAP) can prove to be a significant treatment option as endogenous compounds which may have remarkable innate advantage showing maximum ‘biological relevance’. Graphical abstract

Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury

2017 ◽  
Vol 22 (04) ◽  
pp. 464-471 ◽  
Author(s):  
Wayne A. Chen ◽  
T. David Luo ◽  
Jonathan C. Barnwell ◽  
Thomas L. Smith ◽  
Zhongyu Li
Keyword(s):  
Young Adult ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Adolescent And Young Adult ◽  
Post Injury ◽  
Adult Rats ◽  
Regulatory Factors

Background: Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion. Methods: Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period. Results: Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance. Conclusions: The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

2013 ◽  
Vol 119 (3) ◽  
pp. 720-732 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Ranjan Gupta ◽  
Allan D. Levi
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Fluorescent Protein ◽  
Control Groups ◽  
Myelinated Axons ◽  
Segmental Nerve ◽  
Green Fluorescent

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

scholarly journals Erythropoietin Accelerates Functional Recovery After Peripheral Nerve Injury

2008 ◽  
Vol 90 (8) ◽  
pp. 1644-1653 ◽  
Author(s):  
John C Elfar ◽  
Justin A Jacobson ◽  
J Edward Puzas ◽  
Randy N Rosier ◽  
Michael J Zuscik
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury

Gene transfer to schwann cells after peripheral nerve injury: A delivery system for therapeutic agents

1998 ◽  
Vol 43 (2) ◽  
pp. 205-211 ◽  
Author(s):  
Jesper Sørensen ◽  
Georg Haase ◽  
Christian Krarup ◽  
Helene Gilgenkrantz ◽  
Axel Kahn ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Delivery System ◽  
Peripheral Nerve Injury ◽  
Therapeutic Agents

scholarly journals The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration.

1987 ◽  
Vol 165 (4) ◽  
pp. 1218-1223 ◽  
Author(s):  
V H Perry ◽  
M C Brown ◽  
S Gordon
Keyword(s):  
Optic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerves ◽  
Peripheral Nerve Injury ◽  
Macrophage Response ◽  
Large Numbers ◽  
Myelin Degradation ◽  
Degenerating Axons

Using mAbs and immunocytochemistry we have examined the response of macrophages (M phi) after crush injury to the sciatic or optic nerve in the mouse and rat. We have established that large numbers of M phi enter peripheral nerves containing degenerating axons; the M phi are localized to the portion containing damaged axons, and they phagocytose myelin. The period of recruitment of the M phi in the peripheral nerve is before and during the period of maximal proliferation of the Schwann cells. In contrast, the degenerating optic nerve attracts few M phi, and the removal of myelin is much slower. These results show the clearly different responses of M phi to damage in the central and peripheral nervous systems, and suggest that M phi may be an important component of subsequent repair as well as myelin degradation.

Regeneration and functional recovery following peripheral nerve injury

2004 ◽  
Vol 1 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Francisco J. Rodríguez ◽  
Antoni Valero-Cabré ◽  
Xavier Navarro
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury

Sustained IGF-1 delivery ameliorates effects of chronic denervation and improves functional recovery after peripheral nerve injury

Biomaterials ◽  
2021 ◽  
pp. 121244
Author(s):  
Philip J. Hanwright ◽  
Chenhu Qiu ◽  
Jennifer Rath ◽  
Yang Zhou ◽  
Nicholas von Guionneau ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Chronic Denervation

scholarly journals Functional Recovery via Preregenerated Nerve Graft in Rat Sciatic Nerve Injury Model

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Umang Khandpur ◽  
Ying Yan ◽  
Wilson Zachary Ray ◽  
Matthew R MacEwan
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Muscle Force ◽  
Nerve Graft ◽  
Tissue Loss ◽  
Limb Amputation ◽  
Percent Recovery

Abstract INTRODUCTION Patients who have experienced major tissue loss with peripheral nerve injury (eg, limb amputation) may be offered composite tissue allotransplantation (CTA). The return of sensory ability and cosmetic component of CTAs make them an attractive alternative to prosthetic devices. Unfortunately, robust reinnervation especially over great distances remains an issue for hand allotransplants. In this study, we introduce a preregenerated nerve graft to shorten the distance and therefore time to terminal tissue reinnervation, which could improve the utility of CTAs. METHODS A total of 18 rats weighing 250 to 300 gm each were randomized into 1 of 3 groups: baseline, fresh, or preregenerated. The baseline group underwent sham surgery to obtain baseline functional data. The fresh and preregenerated groups both underwent grafting of the sciatic nerve but the preregenerated group utilized 8-wk preregenerated grafts. At postperative week 8 from distal neurorrhaphy, both groups underwent terminal functional testing via EMG and evoked muscle force. RESULTS The preregenerated group had significantly greater mean EMG (P < .05) and maximum tetanic muscle force values (P < .05) than the fresh group. Mean percent recovery in EMG for the fresh group was 21.95% compared with 81.79% in the preregenerated group. Mean percent recovery in muscle force was 9.46% and 33.15%, respectively. CONCLUSION The results of this study provide a novel approach to enhance final functional recovery after peripheral nerve injury. The current practice of constructing a nerve stump may be improved by grafting a nerve segment at the time of injury and allowing it to preregenerate into local musculature so that if a CTA is later performed, an expedited and more robust reinnervation could be accomplished.

Use of the CatWalk gait analysis system to assess functional recovery in rodent models of peripheral nerve injury – a systematic review

2020 ◽  
Vol 345 ◽  
pp. 108889
Author(s):  
Johannes Heinzel ◽  
Gregor Längle ◽  
Viola Oberhauser ◽  
Thomas Hausner ◽  
Jonas Kolbenschlag ◽  
...  
Keyword(s):  
Systematic Review ◽  
Peripheral Nerve ◽  
Gait Analysis ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Rodent Models ◽  
Analysis System
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