scholarly journals Combining reverse end-to-side neurorrhaphy with rapamycin treatment on chronically denervated muscle in rats

2021 ◽  
Vol 20 (2) ◽  
pp. 359
Author(s):  
Yijian Chen ◽  
Wanqiong Yuan ◽  
Xiaolong Zeng ◽  
Yuanchen Ma ◽  
Qiujian Zheng ◽  
...  
2020 ◽  
pp. 1-8
Author(s):  
Ranjan Gupta ◽  
Justin P. Chan ◽  
Jennifer Uong ◽  
Winnie A. Palispis ◽  
David J. Wright ◽  
...  

OBJECTIVECurrent management of traumatic peripheral nerve injuries is variable with operative decisions based on assumptions that irreversible degeneration of the human motor endplate (MEP) follows prolonged denervation and precludes reinnervation. However, the mechanism and time course of MEP changes after human peripheral nerve injury have not been investigated. Consequently, there are no objective measures by which to determine the probability of spontaneous recovery and the optimal timing of surgical intervention. To improve guidance for such decisions, the aim of this study was to characterize morphological changes at the human MEP following traumatic nerve injury.METHODSA prospective cohort (here analyzed retrospectively) of 18 patients with traumatic brachial plexus and axillary nerve injuries underwent biopsy of denervated muscles from the upper extremity from 3 days to 6 years after injury. Muscle specimens were processed for H & E staining and immunohistochemistry, with visualization via confocal and two-photon excitation microscopy.RESULTSImmunohistochemical analysis demonstrated varying degrees of fragmentation and acetylcholine receptor dispersion in denervated muscles. Comparison of denervated muscles at different times postinjury revealed progressively increasing degeneration. Linear regression analysis of 3D reconstructions revealed significant linear decreases in MEP volume (R = −0.92, R2 = 0.85, p = 0.001) and surface area (R = −0.75, R2 = 0.56, p = 0.032) as deltoid muscle denervation time increased. Surprisingly, innervated and structurally intact MEPs persisted in denervated muscle specimens from multiple patients 6 or more months after nerve injury, including 2 patients who had presented > 3 years after nerve injury.CONCLUSIONSThis study details novel and critically important data about the morphology and temporal sequence of events involved in human MEP degradation after traumatic nerve injuries. Surprisingly, human MEPs not only persisted, but also retained their structures beyond the assumed 6-month window for therapeutic surgical intervention based on previous clinical studies. Preoperative muscle biopsy in patients being considered for nerve transfer may be a useful prognostic tool to determine MEP viability in denervated muscle, with surviving MEPs also being targets for adjuvant therapy.


2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.


1988 ◽  
Vol 255 (6) ◽  
pp. E850-E856 ◽  
Author(s):  
R. R. Almon ◽  
D. C. Dubois

This report describes changes in muscle mass of innervated and denervated pairs of muscles taken from intact and adrenalectomized 250-g male Sprague-Dawley rats provided with different diets. Diets ranged from a nutritionally complete liquid diet to starvation (water only). In the intact animals, muscles with a more tonic character (soleus) are less sensitive to starvation than are muscles with a more phasic character (extensor digitorum longus), whereas the opposite is true of denervation. In the intact animals, starvation greatly increased the amount of atrophy following denervation. In the adrenalectomized animals, starvation had no effect on the amounts of atrophy following denervation. Furthermore, adrenalectomy virtually eliminated the fiber-type differences in the amount of atrophy following denervation. In addition, a comparison between denervated muscles from intact animals and adrenalectomized animals subjected to starvation demonstrates that all denervated muscles from the adrenalectomized animals atrophy less. Finally, it was observed that although an adrenalectomized animal can tolerate 6 days of starvation, an adrenalectomized-castrated animal cannot tolerate even short periods of starvation. The difference appears to be due to low amounts of corticosterone of testicular origin.


Hand ◽  
2021 ◽  
pp. 155894472199246
Author(s):  
David D. Rivedal ◽  
Meng Guo ◽  
James Sanger ◽  
Aaron Morgan

Targeted muscle reinnervation (TMR) has been shown to improve phantom and neuropathic pain in both the acute and chronic amputee population. Through rerouting of major peripheral nerves into a newly denervated muscle, TMR harnesses the plasticity of the brain, helping to revert the sensory cortex back toward the preinsult state, effectively reducing pain. We highlight a unique case of an above-elbow amputee for sarcoma who was initially treated with successful transhumeral TMR. Following inadvertent nerve biopsy of a TMR coaptation site, his pain returned, and he was unable to don his prosthetic. Revision of his TMR to a more proximal level was performed, providing improved pain and function of the amputated arm. This is the first report to highlight the concept of secondary neuroplasticity and successful proximal TMR revision in the setting of multiple insults to the same extremity.


Author(s):  
A. Marcante ◽  
R. Zanato ◽  
M. Ferrero ◽  
S. Zampieri ◽  
H. Kern ◽  
...  

Sarcoma ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaodong Mu ◽  
Christian Isaac ◽  
Trevor Schott ◽  
Johnny Huard ◽  
Kurt Weiss

Osteosarcoma (OS) is the most common primary malignancy of bone. Mortality is determined by the presence of metastatic disease, but little is known regarding the biochemical events that drive metastases. Two murine OS cell lines, K7M2 and K12, are related but differ significantly in their metastatic potentials: K7M2 is highly metastatic whereas K12 displays much less metastatic potential. Using this experimental system, the mammalian target of rapamycin (mTOR) pathway has been implicated in OS metastasis. We also discovered that aldehyde dehydrogenase (ALDH, a stem cell marker) activity is higher in K7M2 cells than K12 cells. Rapamycin treatment reduces the expression and enzymatic activity of ALDH in K7M2 cells. ALDH inhibition renders these cells more susceptible to apoptotic death when exposed to oxidative stress. Furthermore, rapamycin treatment reduces bone morphogenetic protein-2 (BMP2) and vascular endothelial growth factor (VEGF) gene expression and inhibits K7M2 proliferation, migration, and invasionin vitro. Inhibition of ALDH with disulfiram correlated with decreased mTOR expression and activity. In conclusion, we provide evidence for interaction between mTOR activity, ALDH activity, and metastatic potential in murine OS cells. Our work suggests that mTOR and ALDH are therapeutic targets for the treatment and prevention of OS metastasis.


1997 ◽  
Vol 13 (05) ◽  
pp. 337-343 ◽  
Author(s):  
Nicolas Hynes ◽  
James Bain ◽  
Achilleas Thoma ◽  
Karen Veltri ◽  
John Maguire
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