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

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.

Author(s):  
Samyak Pandey ◽  
Jayesh Mudgal

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


Brain ◽  
2009 ◽  
Vol 132 (8) ◽  
pp. 2180-2195 ◽  
Author(s):  
Daria Guseva ◽  
Doychin N. Angelov ◽  
Andrey Irintchev ◽  
Melitta Schachner

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

2004 ◽  
Vol 1 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Francisco J. Rodríguez ◽  
Antoni Valero-Cabré ◽  
Xavier Navarro

Biomaterials ◽  
2021 ◽  
pp. 121244
Author(s):  
Philip J. Hanwright ◽  
Chenhu Qiu ◽  
Jennifer Rath ◽  
Yang Zhou ◽  
Nicholas von Guionneau ◽  
...  

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Umang Khandpur ◽  
Ying Yan ◽  
Wilson Zachary Ray ◽  
Matthew R MacEwan

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.


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