Acetylcholine receptors of the neuromuscular junctions present normal distribution after peripheral nerve injury and repair through nerve guidance associated with fibrin biopolymer

Leite, Ana Paula; Pinto, Carina Guidi; Tibúrcio, Felipe Cantore; Muller, Kevin Silva; Padovani, Carlos Roberto; Barraviera, Benedito; Ferreira, Rui Seabra; Leal, Claudenete Vieira; Matsumura, Cíntia Yuri; Matheus, Selma Maria Michelin

doi:10.1016/j.injury.2022.11.047

Cited by 6 publications

(12 citation statements)

References 57 publications

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“…These results complement previous research carried out by our group, confirming that HFB can reduce the number of required suture stitches 9 and improves morphological and molecular recovery of NMJs, 8,64 thus potentiating axonal 9 and neuromuscular 64 regeneration.…”

Section: Discussionsupporting

confidence: 90%

“…59 The Feret angle describes the elongation degree of the delimited area, [59][60][61] suggesting that the NMJs in the SB group were more circular and closer to a pretzel-like shape, which is their normal morphological pattern. 62,63 These results complement previous research carried out by our group, confirming that HFB can reduce the number of required suture stitches 9 and improves morphological and molecular recovery of NMJs, 8,64 thus potentiating axonal 9 and neuromuscular 64 regeneration.…”

Section: Discussionsupporting

confidence: 88%

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Neuroregeneration and immune response after neurorrhaphy are improved with the use of heterologous fibrin biopolymer in addition to suture repair alone

et al. 2023

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Introduction/Aims: Peripheral nerve injuries result in impaired neuromuscular interactions, leading to morphological and functional alterations. Adjuvant suture repair methods have been used to improve nerve regeneration and modulate the immune response. Heterologous fibrin biopolymer (HFB), a scaffold with adhesive properties, plays a critical role in tissue repair. The aim of this study is to evaluate neuroregeneration and immune response focusing on neuromuscular recovery, using sutureassociated HFB for sciatic nerve repair.Methods: Forty adult male Wistar rats were distributed into four groups (n = 10): C (control), only sciatic nerve location; D (denervated), neurotmesis and 6-mm gap removal and fixation stumps in subcutaneous tissue; S (suture), neurotmesis followed by suture; and SB (suture + HFB), neurotmesis followed by suture and HFB. Analysis of M2 macrophages (CD206 + ), as well as the morphology and morphometry of nerves, soleus muscle, and neuromuscular junctions (NMJs), were performed at 7 and 30 days after surgery. Results:The SB group had the highest M2 macrophage area in both periods. After 7 days, SB was the only group similar to the C group regarding the number of axons; furthermore, after 30 days, the SB group was closer to the C group concerning blood vessel and central myonuclear numbers, NMJ angle, and connective tissue volume.After 7 days, increases in nerve area, as well as the number and area of blood vessels, were also observed in SB.Discussion: HFB potentiates the immune response, increases axonal regeneration, induces angiogenesis, prevents severe muscle degeneration, and assists in NMJ recovery. In conclusion, suture-associated HFB has major implications for improved peripheral nerve repair.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

Neuroregeneration and immune response after neurorrhaphy are improved with the use of heterologous fibrin biopolymer in addition to suture repair alone

et al. 2023

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“…The technique used in this work to visualize the NMJs was the “nonspecific esterase” method, 26 which is based on the marking of positive esterase sites that contain ACh, leading to visualization of the entire NMJ morphology. Therefore, “specific” techniques for labeling nAChRs, such as α‐bungarotoxin, 40 would have enabled a better visualization and understanding of the possible remodeling of these receptors. Furthermore, the enlargement of the NMJs may be related to cellular proteins other than nAChRs 38,41 …”

Section: Discussionmentioning

confidence: 99%

Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

et al. 2023

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Introduction/Aims The mechanisms that underlie the pathogenesis of statin‐associated muscle symptoms (SAMS) remain unclear. Pregnancy is associated with increased cholesterol levels. Statins may be useful during pregnancy, but their safety is uncertain. Hence, we investigated the postpartum effects of exposure to rosuvastatin and simvastatin during pregnancy in Wistar rats, targeting the neuromuscular structures. Methods Twenty‐one pregnant Wistar rats were divided into three groups: control (C) treated with vehicle (dimethylsulfoxide + dH20), simvastatin (S) 62.5 mg/kg/day, and rosuvastatin (R) 10 mg/kg/day. Gavage was performed daily from the gestational days 8 to 20. At weaning, the postpartum mother tissues were collected and subjected to morphological and morphometric analysis of the soleus muscle, associated neuromuscular junctions (NMJs), and the sciatic nerve; protein quantification; quantification of the cholesterol and creatine kinase in the serum; and intramuscular collagen analysis. Results An increase in morphometric parameters (area, maximum and minimum diameters, Feret diameter, and minimum Feret) was observed in NMJs from the S and R groups in comparison with the C group, and there was also a loss of common NMJ circularity. The number of myofibers with central nuclei was higher in S (17 ± 3.9, P = .0083) and R (18.86 ± 14.42, P = .0498) than in C (6.8 ± 2.6). Discussion Gestational exposure to statins induced postpartum NMJ morphology alterations in soleus muscle, which may be caused by the remodeling of clusters of nicotinic acetylcholine receptors. This may be associated with the development and progression of SAMS observed in clinical practice.

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“…Denervation also leads to significant changes in the Agrin/LRP4/Musk/Ra pathway, prejudicing the maintenance of nAChR clusters [ 69 ] and leading to alterations of the area and conformation of the NMJ [ 10 ]. Shortly after injury proteins of this pathway have increased synthesis but its complex disorganization leads to failure in proper function, inactivation of MMP3, and accumulation of Agrin in the synaptic cleft [ 28 ].…”

Section: Pathophysiology Of Nerve Injurymentioning

confidence: 99%

“…The use of HFB as an adjunct in peripheral and central nerve reconstruction has been showing promising results through the development of an immunomodulatory and neuroprotective environment at the injury site [ 10 - 13 ] and has also been applied in various other experimental models of reconstructive surgery [ 7 , 14 ]. The use of HFB has already been experimentally shown to provide a microenvironment of stability and protection at the reconstruction site, leading to positive scenarios of nerve regeneration.…”

Section: Introductionmentioning

confidence: 99%

Heterologous fibrin biopolymer as an emerging approach to peripheral nerve repair: a scoping review

Muller,

Tibúrcio,

Ferreira Junior

et al. 2024

J. Venom. Anim. Toxins incl. Trop. Dis

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Nerve injuries present a substantial challenge within the medical domain due to their prevalent occurrence and significant impact. In nerve injuries, a range of physiopathological and metabolic responses come into play to stabilize and repair the resulting damage. A critical concern arises from the disruption of connections at neuromuscular junctions, leading to profound degeneration and substantial loss of muscle function, thereby hampering motor tasks. While end-to-end neurorrhaphy serves as the established technique for treating peripheral nerve injuries, achieving comprehensive morphofunctional recovery remains a formidable challenge. In pursuit of enhancing the repair process, alternative and supportive methods are being explored. A promising candidate is the utilization of heterologous fibrin biopolymer, a sealant devoid of human blood components. Notably, this biopolymer has showcased its prowess in establishing a stable and protective microenvironment at the site of use in multiple scenarios of regenerative medicine. Hence, this scoping review is directed towards assessing the effects of associating heterologous fibrin biopolymer with neurorrhaphy to treat nerve injuries, drawing upon findings from prior studies disseminated through PubMed/MEDLINE, Scopus, and Web of Science databases. Further discourse delves into the intricacies of the biology of neuromuscular junctions, nerve injury pathophysiology, and the broader utilization of fibrin sealants in conjunction with sutures for nerve reconstruction procedures. The association of the heterologous fibrin biopolymer with neurorrhaphy emerges as a potential avenue for surmounting the limitations associated with traditional sealants while also mitigating degeneration in nerves, muscles, and NMJs post-injury, thereby fostering a more conducive environment for subsequent regeneration. Indeed, queries arise regarding the long-term regenerative potential of this approach and its applicability in reconstructive surgeries for human nerve injuries.

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Acetylcholine receptors of the neuromuscular junctions present normal distribution after peripheral nerve injury and repair through nerve guidance associated with fibrin biopolymer

Cited by 6 publications

References 57 publications

Neuroregeneration and immune response after neurorrhaphy are improved with the use of heterologous fibrin biopolymer in addition to suture repair alone

Neuroregeneration and immune response after neurorrhaphy are improved with the use of heterologous fibrin biopolymer in addition to suture repair alone

Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

Heterologous fibrin biopolymer as an emerging approach to peripheral nerve repair: a scoping review

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