The functional outcome after peripheral nerve repair is often unpredictable for many reasons, e.g., the severity of neuronal death and scarring. Axonal degeneration significantly affects outcomes. ...Post-injury axonal degeneration in peripheral nerves is accompanied by myelin degradation initiated by Schwann cells (SCs), which activate autophagy, a ubiquitous cytoprotective process essential for degrading and recycling cellular constituents. Scar formation occurs concomitantly with nerve insult and axonal degeneration. The association between SC autophagy and the mechanisms of nerve scar formation is still unknown. A rat model of peripheral nerve lesions induced by sciatic nerve transection injuries was used to examine the function of autophagy in fibrosis reduction during the early phase of nerve repair. Rats were treated with rapamycin (autophagy inducer) or 3-methyladenine (autophagy inhibitor). One week after the nerve damage, fibrosis was potently inhibited in rapamycin-treated rats and, based on gait analysis, yielded a better functional outcome. Immunohistochemistry showed that the autophagic activity of SCs and the accumulation of neurofilaments were upregulated in rapamycin-treated rats. A deficiency of SC autophagic activity might be an early event in nerve scar formation, and modulating autophagy might be a powerful pharmacological approach for improving functional outcomes.
Wen-Bin Yeh,1 Wei-Kai Lee,2,3 Mei-Chia Chou,4 I-Ming Jou5 1Emergency department, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 2Emergency Department, Sinying Hospital, Ministry of Health ...and Welfare, Tainan, Taiwan; 3Min-Hwei Junior College of Health Care Management, Tainan, Taiwan; 4Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Pingtung County, Taiwan; 5Department of Orthopedics, E-Da Hospital, Kaohsiung, Taiwan Correspondence: I-Ming Jou, Department of Orthopedics, E-Da Hospital, No. 1, Yida Road, Yanchao Dist, Kaohsiung City, 82445, Taiwan, Email email protected Mei-Chia Chou, Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Pingtung Branch, No.1. Anping Lane 1. Jausheng Rd., Neipu Shiang, Pingtung County, Taiwan, Email email protected View the original paper by Dr Wei and colleagues
Apoptosis has emerged as a primary cause of tendinopathy. CD44 signaling pathways exert anti-apoptotic and -inflammatory effects on tumor cells, chondrocytes, and fibroblast-like synoviocytes. The ...aim of this study was to examine the association among CD44, apoptosis, and inflammation in tendinopathy. Expression of CD44 and apoptotic cell numbers in tendon tissue from patients with long head of biceps (LHB) tendinopathy were determined according to the histological grades of tendinopathy. Primary tenocytes from Achilles tendon of Sprague–Dawley rats 1 week after collagenase injection were cultured with an antagonizing antibody against CD44. Treatment responses were determined by evaluating cell viability and expression of tendon-related proliferation markers, inflammatory mediators, and apoptosis. The expression of CD44 and apoptosis were positively correlated with the severity of tendinopathy in the human LHB tendinopathy. Furthermore, CD44 expression and apoptotic cells were co-stained in tendinopathic tendon. Blocking the CD44 signaling pathways in rat primary tenocytes by OX-50 induced cell apoptosis and the elevated levels of cleaved caspase-3. Furthermore, they had decreased cell viability and expression of collagen type I, type III, tenomodulin, and phosphorylated AKT. In contrast, there were elevated levels of inflammatory mediators, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, and phosphorylated NF-κB, as well as matrix metalloproteinase (MMP) family members including MMP-1, -3, -9, and -13 in tenocytes upon OX-50 treatment. This study is the first to demonstrate the association of CD44 and apoptosis in tendinopathy. Our data imply that CD44 may play a role in tendinopathy via regulating apoptosis, inflammation, and extracellular matrix homeostasis.
Abstract Spinal cord injury (SCI) often results in some form of paralysis. Recently, SCI therapy has been focused on preventing secondary injury to reduce both neuroinflammation and lesion size so ...that functional outcome after an SCI may be improved. Previous studies have shown that adenosine receptors (AR) are a major regulator of inflammation after an SCI. The current study was performed to examine the effect of caffeine, a pan-AR blocker, on spontaneous functional recovery after an SCI. Animals were assigned into 3 groups randomly, including sham, PBS and caffeine groups. The rat SCI was generated by an NYU impactor with a 10 g rod dropped from a 25 mm height at thoracic 9 spinal cord level. Caffeine and PBS were injected daily during the experiment period. Hind limb motor function was evaluated by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale at 1 week and 4 weeks after the SCI. Spinal cord segments were collected after final behavior evaluation for morphological analysis. The tissue sparing was evaluated by luxol fast blue staining. Immunofluorescence stain was employed to assess astrocyte activation and neurofilament positioning, while microglia activation was examined by immunohistochemistry stain.The results showed that spontaneous functional recovery was blocked after the animals were subjected caffeine daily. Moreover, caffeine administration increased the demyelination area, promoted astrocyte and microglia activation and decreased the quantity of neurofilaments. These findings suggest that the neurotoxicity effect of caffeine may be associated with the inhibition of neural repair and the promotion of neuroinflammation.
Arthroscopic resection has become a favorable alternative for wrist ganglions. However, for recurrent wrist ganglions, arthroscopic resection is relatively contraindicated. The purpose of this study ...was to evaluate the clinical outcomes of arthroscopic resection for recurrent wrist ganglions and to identify their safety and efficacy.
From June 2011 to February 2017, 17 patients with recurrent wrist ganglion were treated with arthroscopic resection. We evaluated the visual analog scale, modified Mayo wrist score, and Disabilities of Arm, Shoulder and Hand Outcome Measure preoperatively and at the final follow-up. Patients were questioned for pain reduction, pain during pushups, and any difficulty in returning to work. Recurrence and complications were also assessed at each follow-up visit.
We enrolled 17 patients and median follow-up was 58 months. The reduction in pain was significant. Only 2 of the 17 patients had residual pain after arthroscopic resection. One female patient showed recurrences 3 years later. Although 2 cases of stiffness were noted after the operation, no significant complication was present 3 months postoperatively. Most patients had good recovery and could resume work; however, 2 patients reported fair recovery.
The results of this study confirmed that arthroscopic excision could be an effective and safe treatment for recurrent ganglions; therefore, should not be contraindicated for treating recurrent wrist ganglions. Nevertheless, further prospective studies with larger patient numbers are needed to establish a stronger evidence for arthroscopic resection of recurrent wrist ganglions.
The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this ...combination in treating tendinopathy has been reported. We hypothesized that the specific formulations of cHA and dexamethasone (DEX) conferred amelioration of tendinopathy via anti-apoptosis and anti-senescence. In this controlled laboratory study, primary tenocytes from the human tendinopathic long head of biceps were treated with three cHA formulations (cHA:linealized HA = 80:20, 50:50, and 20:80) + DEX with or without IL-1β stimulation. Cell viability, inflammatory cytokines, tendon-related proliferation markers, matrix metalloproteinases (MMPs), senescent markers, and apoptosis were examined. The in vivo therapeutic effects of the selected cHA + DEX combinations were evaluated in a collagenase-induced rat patellar tendinopathy model. The expression levels of inflammatory mediators, including IL-1β, IL-6, COX-2, MMP-1, and MMP-3 were significantly reduced in all cHA + DEX-treated tenocytes (p < 0.05, all). The cHA (50:50) + DEX and cHA (20:80) + DEX combinations protected tenocytes from cytotoxicity, senescence, and apoptosis induced by DEX in either IL-1β stimulation or none. Furthermore, the two combinations significantly improved the rat experimental tendinopathy by reducing ultrasound feature scores and histological scores as well as the levels of apoptosis, senescence, and senescence-associated secretory phenotypes (p < 0.05, all). We identified two specific cHA formulations (cHA (50:50) and cHA (20:80)) + DEX that could ameliorate tendinopathy through anti-senescence and -apoptosis without cytotoxicity. This study provides a possible approach to treating tendinopathy using the combination of two well-known agents.
De Quervain's disease, carpal tunnel syndrome (CTS), and trigger finger (digit) are three common pathological conditions of the hand. They are considered overuse syndromes and occur predominantly in ...females. The prevalence rate and cause-specific risks of these three tendinopathies have not yet been clarified. Data from 41,871 cases listed in the Taiwan National Health Insurance Research Database (NHIRD) from 2010 to 2014 were analyzed. The prevalence rate of these 3 conditions by age, sex, and the risk factors of female-dominant diseases (e.g., osteoporosis, rheumatoid arthritis RA, and tendinopathy), diabetes mellitus, and hormone antagonist treatment was evaluated. We found that 1.59% of the population developed CTS, 0.49% developed de Quervain's, and 1.07% developed trigger finger. Cases were more likely to develop the three hand tendinopathies if they were female, between 50 and 59 years old, and, according to a multivariate analysis, comorbid with RA, diabetes, using hormone antagonists. Our findings should provide an understanding of the risk factors associated with hand tendinopathy.
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