Peripheral nerve regeneration through allografts compared with autografts in FK506-treated monkeys

2006 ◽  
Vol 105 (4) ◽  
pp. 602-609 ◽  
Author(s):  
Cristina Aubá ◽  
Bernardo Hontanilla ◽  
Juan Arcocha ◽  
Óscar Gorría

Object The clinical use of nerve allografts combined with immunosuppressant therapy has become a genuine possibility that could supersede the classic use of autografts. However, contradictory data have been reported on whether immunosuppressant therapy should be temporarily administered. The purpose of this study was to compare the nerve regeneration obtained using ulnar nerve allografts in nonhuman primates temporarily treated with FK506 (tacrolimus) with that obtained using nerve autografts. Methods Four-centimeter nerve autografts or allografts were placed in the distal ulnar motor nerve of eight monkeys. The FK506 was temporarily administered to the animals of the allograft group for 2 months. At periods of 3, 5, and 8 months postsurgery, quantitative electrophysiological recordings were obtained to estimate muscle response. A quantitative analysis of ulnar motor neurons in the spinal cord was performed and axons were counted stereologically. No statistically significant differences were found in the neuronal and axonal counts between autograft and allograft groups at 8 months. The electrophysiological studies showed no differences relative to the amplitude, but the autograft group presented with a greater nerve conduction velocity (NCV). However, no statistically significant differences were found between the number of neurons and distal axonal counts in the two groups. Conclusions Nerve regeneration through cold-preserved allografts in a primate model temporarily treated with FK506 was similar to that obtained using nerve autografts, in terms of neuronal and axonal counts. Nevertheless, temporary immunosuppression produced lower NCV when allografts were used, with less maturation of the myelinated fibers, which indicated that a partial rejection had taken place.

1987 ◽  
Vol 12 (2) ◽  
pp. 211-217
Author(s):  
MARIE A. BADALAMENTE ◽  
L. C. HURST ◽  
S. B. PAUL ◽  
A. STRACHER

This investigation describes the use of the calcium-activated protease inhibitor, leupeptin, as an adjunctive therapy to the microsurgical repair of median nerves in a primate model. Our results indicate that leupeptin facilitates morphological recovery in denervated thenar muscles and in distal sensory and mixed motor-sensory nerve trunks and functional recovery measured by motor nerve conduction velocity. Toxicological testing of leupeptin showed that, when administered at a dose of 12mg/kg, intramuscularly, once daily, haematological and clotting profiles were not adversely affected.


2020 ◽  
Vol 232 (06) ◽  
pp. 331-333
Author(s):  
Marko Kavčič ◽  
Aida Zečkanović ◽  
Janez Jazbec ◽  
Marusa Debeljak

IntroductionVincristine is at the core of many treatment protocols for childhood malignancies. The major dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN) which may cause morbidity and disrupt curative treatment. Several studies have tried to identify pharmacogenetic biomarkers for susceptibility to vincristine-induced toxicity (Egbelakin A et al., Pediatr Blood Cancer 2011; 56: 361–367. Aplenc R et al., Br J Haematol 2003; 122: 240–244. Diouf B et al., JAMA 2015; 313: 815–823. Zgheib NK et al., Pharmacogenet Genomics, 2018; 28: 189–195. Gutierrez-Camino A et al., Pharmacogenet Genomics 2016; 26: 100–102. Wright GE et al., Clin Pharmacol Ther 2019; 105: 402–410. Kayilioğlu H et al., J Pediatr Hematol Oncol 2017; 39(6): 458–462). A major limitation of these studies is that VIPN is difficult to measure objectively using only clinical examination and clinical scales. This is especially true for children, who are often unable to report or grade symptoms such as paresthesia, numbness, and pain. Furthermore, some studies are questioning the validity of currently available neuropathy grading scales (Postma TJ et al., Ann Oncol 1998; 9: 739–744). Our group recently showed that electrophysiological studies can be used with great accuracy for early detection of VIPN (Kavcic M et al., J Pediatr Hematol Oncol 2017; 39: 266–271). In the previous study, we found that VIPN presents with primary axonal involvement and is more pronounced on motor neurons (Kavcic M et al., J Pediatr Hematol Oncol 2017; 39: 266–271).


2007 ◽  
Vol 137 (2_suppl) ◽  
pp. P213-P213
Author(s):  
Arash Moradzadeh ◽  
Gregory Howard Borschel ◽  
Christopher Mead Nichols ◽  
Jason Koob ◽  
Daniel Arthur Hunter ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142786 ◽  
Author(s):  
Hideki Yagi ◽  
Bisei Ohkawara ◽  
Hiroaki Nakashima ◽  
Kenyu Ito ◽  
Mikito Tsushima ◽  
...  

2017 ◽  
Vol 33 (08) ◽  
pp. 549-556 ◽  
Author(s):  
Marcela Fernandes ◽  
Sandra Valente ◽  
João Santos ◽  
Rebeca Furukawa ◽  
Carlos Fernandes ◽  
...  

Background Peripheral nerves have limited regeneration capacity despite best efforts. Platelet-rich fibrin (PRF) contains growth factors that may stimulate peripheral nerve regeneration. This study verified whether nerve regeneration using autogenous vein conduits filled with PRF is comparable to autologous nerve graft, which is the standard treatment. Methods The sciatic nerve of the right paw of inbred rats was dissected, and a 10-mm segment was removed from rats randomized to receive autologous nerve graft (GRAFT) or vein conduit filled with PRF (PRF). A third group (SHAM) underwent surgery without nerve resection. The sciatic functional index (SFI) was measured 0, 30, 60, and 90 days postsurgery. Morphometry and morphology of the distal nerve injury were examined. Motor neurons in the anterior horn of spinal cord stained with FluoroGold and counted. Results No significant difference in SFI was observed between the GRAFT and PRF groups at any time point (all p > 0.05); however, SFI was lower in both groups compared with SHAM (p < 0.05). Morphometric and morphologic indexes were not significantly different between the GRAFT and PRF groups (p > 0.05); however, nerve fibers, axons, and myelin sheaths were thinner in both groups compared with SHAM (p = 0.0001). Average motor neurons' count was similar between the GRAFT and PRF groups (p = 0.91); the count was lower in both groups compared with SHAM (p = 0.002 and p = 0.001), respectively. Conclusion Autologous nerve GRAFT and PRF-filled autogenous vein conduits were associated with similar outcomes, and worse than those observed in SHAM controls. Vein conduits filled with PRF may be a favorable alternative treatment to nerve grafts.


Neuroglia ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 57-67
Author(s):  
Cecilia Pankau ◽  
Shelby McCubbin ◽  
Robin L. Cooper

Glia, or glial cells, are considered a vital component of the nervous system, serving as an electrical insulator and a protective barrier from the interstitial (extracellular) media. Certain glial cells (i.e., astrocytes, microglia, and oligodendrocytes) within the CNS have been shown to directly affect neural functions, but these properties are challenging to study due to the difficulty involved with selectively-activating specific glia. To overcome this hurdle, we selectively expressed light-sensitive ion channels (i.e., channel rhodopsin, ChR2-XXL) in glia of larvae and adult Drosophila melanogaster. Upon activation of ChR2, both adults and larvae showed a rapid contracture of body wall muscles with the animal remaining in contracture even after the light was turned off. During ChR2-XXL activation, electrophysiological recordings of evoked excitatory junction potentials within body wall muscles of the larvae confirmed a train of motor nerve activity. Additionally, when segmental nerves were transected from the CNS and exposed to light, there were no noted differences in quantal or evoked responses. This suggests that there is not enough expression of ChR2-XXL to influence the segmental axons to detect in our paradigm. Activation of the glia within the CNS is sufficient to excite the motor neurons.


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