Role of the Notch Signaling Pathway in Fibrosis of Denervated Skeletal Muscle.

In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 µmol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.

Transposition of branches of radial nerve innervating supinator to posterior interosseous nerve for functional reconstruction of finger and thumb extension in 4 patients with middle and lower trunk root avulsion injuries of brachial plexus.

This study aimed to investigate the reconstruction of the thumb and finger extension function in patients with middle and lower trunk root avulsion injuries of the brachial plexus. From April 2010 to January 2015, we enrolled in this study 4 patients diagnosed with middle and lower trunk root avulsion injuries of the brachial plexus via imaging tests, electrophysiological examinations, and clinical confirmation. Muscular branches of the radial nerve, which innervate the supinator in the forearm, were transposed to the posterior interosseous nerve to reconstruct the thumb and finger extension function. Electrophysiological findings and muscle strength of the extensor pollicis longus and extensor digitorum communis, as well as the distance between the thumb tip and index finger tip, were monitored. All patients were followed up for 24 to 30 months, with an average of 27.5 months. Motor unit potentials (MUP) of the extensor digitorum communis appeared at an average of 3.8 months, while MUP of the extensor pollicis longus appeared at an average of 7 months. Compound muscle action potential (CMAP) appeared at an average of 9 months in the extensor digitorum communis, and 12 months in the extensor pollicis longus. Furthermore, the muscle strength of the extensor pollicis longus and extensor digitorum communis both reached grade III at 21 months. Lastly, the average distance between the thumb tip and index finger tip was 8.8 cm at 21 months. In conclusion, for patients with middle and lower trunk injuries of the brachial plexus, transposition of the muscular branches of the radial nerve innervating the supinator to the posterior interosseous nerve for the reconstruction of thumb and finger extension function is practicable and feasible.

Transposition of Branches of Radial Nerve Innervating Supinator to Posterior Interosseous Nerve for Functional Reconstruction of Finger and Thumb Extension in 4 Patients with Middle and Lower Trunk Root Avulsion Injuries of Brachial Plexus / 华中科技大学学报（医学）（英德文版）

This study aimed to investigate the reconstruction of the thumb and finger extension function in patients with middle and lower trunk root avulsion injuries of the brachial plexus.From April 2010 to January 2015,we enrolled in this study 4 patients diagnosed with middle and lower trunk root avulsion injuries of the brachial plexus via imaging tests,electrophysiological examinations,and clinical confirmation.Muscular branches of the radial nerve,which innervate the supinator in the forearm,were transposed to the posterior interosseous nerve to reconstruct the thumb and finger extension function.Electrophysiological findings and muscle strength of the extensor pollicis longus and extensor digitorum communis,as well as the distance between the thumb tip and index finger tip,were monitored.All patients were followed up for 24 to 30 months,with an average of 27.5 months.Motor unit potentials (MUP) of the extensor digitorum communis appeared at an average of 3.8 months,while MUP of the extensor pollicis longus appeared at an average of 7 months.Compound muscle action potential (CMAP) appeared at an average of 9 months in the extensor digitorum communis,and 12 months in the extensor pollicis longus.Furthermore,the muscle strength of the extensor pollicis longus and extensor digitorum communis both reached grade Ⅲ at 21 months.Lastly,the average distance between the thumb tip and index finger tip was 8.8 cm at 21 months.In conclusion,for patients with middle and lower trunk injuries of the brachial plexus,transposition of the muscular branches of the radial nerve innervating the supinator to the posterior interosseous nerve for the reconstruction of thumb and finger extension function is practicable and feasible.

Verapamil inhibits scar formation after peripheral nerve repair in vivo.

The calcium channel blocker, verapamil, has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro. It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue. In this study, the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No. 10-0 suture. The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks. Compared with the control group (stoma wrapped with gelfoam soaked with physiological saline), the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo, suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons. These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.

[Combined immunosuppression of FK506 and RS-61443 in rat limb allotransplantation].

OBJECTIVE: To study the immunosuppressive effect of combined therapy with FK506 and RS-61443 in rat limb allotransplantation. METHODS: A total of 101 male SD rats were randomly divided into seven groups and used as recipients, and 101 Wistar rats were used as donors. All SD rats were performed limb allotransplantation without using immunosuppressants in control group. In experimental groups (Groups 1-6), the recipients were immunosuppressed with various dosages of FK506, RS-61443 or FK506 + RS61443, after transplantation for 5 weeks. To evaluate the results, we observed circulation of the transplanted limb, the mean rejection time, the histologic grading of skin rejection of limb grafts and the survival time of limb grafts. RESULTS: The control group showed rejection signs (edema and erythema of the skin) after a mean time of 3.36 +/- 1.15 days, and the mean survival time of the allografts was only 7.00 +/- 0.78 days. In the groups only using FK506 or RS-61443, the survival time were prolonged to varying degrees, but rejection occurred even in the period of using drug. As dosage increased, the rejection could not be prevented and the damage to liver and kidney could be induced. In the group using FK506 in combination with RS-61443, only skin and muscle of limb allografts showed slight rejection sign, function of liver and kidney was not obviously affected, the mean survival time of limb allografts was prolonged to 58.76 +/- 6.81 days. CONCLUSIONS: A combination of FK506 and RS-61443 is a more potent immunosuppressive agent than FK506 oro RS-61443 in preventing the rejection of limb allografts, and it can obviously prolong the survival time of limb allografts.