Nerve Regeneration
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2021 ◽  
Vol 10 (3) ◽  
pp. 83-90
Author(s):  
N. A. Shchudlo ◽  
T. N. Varsegova ◽  
M. M. Shchudlo

The effect of ageing on the morphofunctional features of nerves and the process of their posttraumatic regeneration has been studied in details. However, it is not known, whether there are differences of the neuroregeneration potential in the young, adult and mature experimental animals.The aim of the study was to evaluate histomorphometrical parameters of the rat sciatic nerve regeneration after cutting and microsurgical suturing depending on their age.Materials and Methods. The study included 15 white laboratory Wistar rats aged 5–6 (young), 8–10 (adult) and 12 months (mature). The sciatic nerve was transected at the level of the middle third of the thigh with microsurgical scissors and sutured with six epi-perineural stitches in the animals. In 4 months the animals were euthanized. Sections of sciatic nerves distal to the levels of sutures were put into araldite, semi-thin slices (0.5–1.0 mkm) were obtained for histomorphometric analysis. Thirteen intact animals were selected as control. Statistical processing was performed using nonparametric methods.Results. The numerical density of endoneural vessels in nerves of operated rats was higher than that in the intact ones, but in mature animals it was significantly lower than in young and adult ones (p<0.001). The numerical density of endoneural cells nuclei in young experimental animals did not differ from that of the intact ones, but in animals from the adult and mature groups it was more than four times higher than in animals from the young group (p<0.001). The numerical density of regenerating myelinated nerve fibers in animals of the young and adult groups did not differ from that of the intact nerve, in animals of the mature group it increased in 2.5 times (p<0.001). The numerical density of degenerating myelinated fibers in the operated animals of experimental groups was higher than in the intact group (two times, six times and 11 times higher, respectively). The diameter distribution of the regenerating myelinated fibers in animals of all groups differed from that of the intact control animals.Conclusions. The data obtained demonstrate a significant decrease in the regenerative potential of Schwann cells and neurons in adult and mature animals compared with the young ones.


2021 ◽  
Author(s):  
Jian Zhang ◽  
Chaochao Li ◽  
Fanqi Meng ◽  
Yanjun Guan ◽  
Tieyuan Zhang ◽  
...  

Abstract Background: Peripheral nerve injury (PNI) is one of the essential causes of physical disability with a high incidence rate. The traditional tissue engineering strategy, Top-Down strategy, has some limitations. A new tissue-engineered strategy, Bottom-Up strategy (tissue-engineered microtissue strategy), has emerged and made significant research progress in recent years. However, to the best of our knowledge, microtissues are rarely used in neural tissue engineering, thus we intended to use microtissues to repair PNI.Methods: We used a low-adhesion cell culture plate to construct adipose-derived mesenchymal stem cells (ASCs) into microtissues in vitro, explored the physicochemical properties and microtissues components, compared the expression of cytokines related to nerve regeneration between microtissues and the same amount of two-dimension (2D)-cultured cells, co-cultured directly microtissues with dorsal root ganglion (DRG) or Schwann cells (SCs) to observe the interaction between them using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA). We used grafts constructed by microtissues and polycaprolactone (PCL) nerve conduit to repair sciatic nerve defects in rats.Results: The present study results indicated that compared with the same number of 2D-cultured cells, microtissue could secrete more nerve regeneration related cytokines to promote SCs proliferation and axons growth. Moreover, in the direct co-culture system of microtissue and DRG or SCs, axons of DRG grown in the direction of microtissue, and there seems to be a cytoplasmic exchange between SCs and ASCs around microtissue. Furthermore, microtissues could repair sciatic nerve defects in rat models more effectively than traditional 2D cultured-ASCs. Conclusion: Tissue-engineered microtissue is an effective strategy for stem cell culture and therapy in nerve tissue engineering.


2021 ◽  
Vol 18 ◽  
pp. 302-308
Author(s):  
Nami Hayakawa ◽  
Hajime Matsumine ◽  
Kaori Fujii ◽  
Hironobu Osaki ◽  
Yoshifumi Ueta ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1301
Author(s):  
Melissa L. D. Rayner ◽  
Jess Healy ◽  
James B. Phillips

The slow rate of neuronal regeneration that follows peripheral nerve repair results in poor recovery, particularly where reinnervation of muscles is delayed, leading to atrophy and permanent loss of function. There is a clear clinical need to develop drug treatments that can accelerate nerve regeneration safely, restoring connections before the target tissues deteriorate irreversibly. The identification that the Rho/Rho-associated kinase (ROCK) pathway acts to limit neuronal growth rate is a promising advancement towards the development of drugs. Targeting Rho or ROCK directly can act to suppress the activity of this pathway; however, the pathway can also be modulated through the activation of upstream receptors; one of particular interest being peroxisome proliferator-activated receptor gamma (PPAR-γ). The connection between the PPAR-γ receptor and the Rho/ROCK pathway is the suppression of the conversion of inactive guanosine diphosphate (GDP)-Rho to active guanosine triphosphate GTP-Rho, resulting in the suppression of Rho/ROCK activity. PPAR-γ is known for its role in cellular metabolism that leads to cell growth and differentiation. However, more recently there has been a growing interest in targeting PPAR-γ in peripheral nerve injury (PNI). The localisation and expression of PPAR-γ in neural cells following a PNI has been reported and further in vitro and in vivo studies have shown that delivering PPAR-γ agonists following injury promotes nerve regeneration, leading to improvements in functional recovery. This review explores the potential of repurposing PPAR-γ agonists to treat PNI and their prospective translation to the clinic.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254968
Author(s):  
Hiroki Tanaka ◽  
Ryosuke Kakinoki ◽  
Yukitoshi Kaizawa ◽  
Hirofumi Yurie ◽  
Ryosuke Ikeguchi ◽  
...  

Previously, we showed silicone nerve conduits containing a vascular bundle and decellularized allogenic basal laminae (DABLs) seeded with bone marrow-derived mesenchymal stem cells (BMSCs) demonstrated successful nerve regeneration. Nerve conduits should be flexible and biodegradable for clinical use. In the current study, we used nerve conduits made of polyglycoric acid (PGA) fiber mesh, which is flexible, biodegradable and capillary-permeable. DABLs were created using chemical surfactants to remove almost all cell debris. In part 1, capillary infiltration capability of the PGA tube was examined. Capillary infiltration into regenerated neural tissue was compared between the PGA tube with blood vessels attached extratubularly (extratubularly vascularized tube) and that containing blood vessels intratubularly (intratubularly vascularized tube). No significant difference was found in capillary formation or nerve regeneration between these two tubes. In part 2, a 20 mm gap created in a rat sciatic nerve model was bridged using the extratubularly vascularized PGA tube containing the DABLs with implantation of isogenic cultured BMSCs (TubeC+ group), that containing the DABLs without implantation of the BMSCs (TubeC- group), and 20 mm-long fresh autologous nerve graft (Auto group). Nerve regeneration in these three groups was assessed electrophysiologically and histomorphometrically. At 24 weeks, there was no significant difference in any electrophysiological parameters between TubeC+ and Auto groups, although all histological parameters in Auto group were significantly greater than those in TubeC+ and TubeC- groups, and TubeC+ group demonstrated significant better nerve regeneration than TubeC- group. The transplanted DABLs showed no signs of immunological rejection and some transplanted BMSCs were differentiated into cells with Schwann cell-like phenotype, which might have promoted nerve regeneration within the conduit. This study indicated that the TubeC+ nerve conduit may become an alternative to nerve autograft.


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