Chondroitinase ABC Administration in Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-analysis.

Introduction: The present systematic review and meta-analysis aims to conduct a comprehensive and complete search of electronic resources to investigate the role of administrating Chondroitinase ABC (ChABC) in improving complications following Spinal Cord Injuries (SCI). Methods: MEDLINE, Embase, Scopus, and Web of Sciences databases were searched until the end of 2019. Two independent reviewers assessed the studies conducted on rats and mice and summarized the data. Using the STATA 14.0 software, the findings were reported as pooled standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 34 preclinical studies were included. ChABC administration improves locomotion recovery after SCI (SMD=0.90; 95% CI: 0.61 to 1.20; P<0.001). The subgroup analysis showed that the differences in the SCI model (P=0.732), the severity of the injury (P=0.821), the number of ChABC administrations (P=0.092), the blinding status (P=0.294), the use of different locomotor score (P=0.567), and the follow-up duration (P=0.750) have no effect on the efficacy of ChABC treatment. Conclusion: The findings of the present study showed that prescribing ChABC has a moderate effect in improving locomotion after SCI in mice and rats. However, this moderate effect introduces ChABC as adjuvant therapy and not as primary therapy.

The effect of chondroitinase ABC and photobiomodulation therapy on neuropathic pain after spinal cord injury in adult male rats.

INTRODUCTION: . The goal of the study was to test the effects of photobiomodulation therapy (PBMT) and intra-spinal injection of chondroitinase ABC (chABC) both alone and combined on pain induced by spinal cord injury (SCI) in rats. MATERIAL AND METHODS: SCI was induced by compression using an aneurysm clip. PBMT used a 660 nm laser starting at 30 minutes after SCI and then daily for 2 week, and at the end of 1-week ChABC was injected into the spinal cord. Allodynia (mechanical and cold), hyperalgesia (mechanical and thermal) and functional recovery were measured. Molecular levels of IL6, BDNF, GDNF and Gad65 were evaluated. RESULTS: . Both ChABC, PBMT and the combination reduced allodynia and thermal hyperalgesia and improved functional recovery, but did not reduce mechanical hyperalgesia. Pain-related factors (BDNF and IL6) were decreased and anti-nociceptive factors (Gad65 and GDNF) were increased. CONCLUSION: . Treatment of SCI by PBM is a non-invasive technique, and could be improved by ChABC injection to reduce neuropathic pain and improve movement.

Effect of vitamins C and E on recovery of motor function after spinal cord injury: systematic review and meta-analysis of animal studies.

CONTEXT: Many animal studies have evaluated the role of vitamins in the recovery of motor function after spinal cord injury, but their results have been contradictory and no consensus has been reached. OBJECTIVE: This meta-analysis aimed to investigate the effects of vitamin C and vitamin E on recovery of motor function after spinal cord injury in animal models. DATA SOURCES: Two authors independently collected the records of relevant articles published in MEDLINE, Embase, Scopus, and Web of Science through November 2018. STUDY SELECTION: All studies conducted in animal models to evaluate the therapeutic effects of vitamin C or vitamin E or both on recovery of motor function after spinal cord injury were included. Studies that lacked a control group or a standard treatment, lacked an assessment of motor function, included genetically modified/engineered animals, included animals pretreated with vitamin C or vitamin E, or combined vitamin treatment with other methods, such as cell therapies, were excluded. DATA EXTRACTION: Data from 10 articles met the inclusion criteria for meta-analysis, conducted in accordance with PRISMA guidelines. RESULTS: Daily supplementation with vitamin C (P < 0.0001) and vitamin E (P < 0.0001) significantly improved the recovery of motor function in animals affected by spinal cord injury. Vitamin C supplementation is effective only when administered intraperitoneally (P < 0.0001). Concurrent supplementation with both vitamins does not show better efficacy than treatment with either one alone. CONCLUSION: Administration of vitamin C and vitamin E in animal models of spinal cord injury significantly improves the recovery of motor function.

Combination of laser and human adipose-derived stem cells in repair of rabbit anal sphincter injury: a new therapeutic approach.

BACKGROUND: Anal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury. DESIGN: Male rabbits were assigned to equal groups (n = 7) including control, sphincterotomy, sphincterotomy treated with laser (660 nm, 90 s, immediately after sphincterotomy, daily, 14 days), hADSCs (2 × 106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser + hADSCs. Ninety days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed. RESULTS: The laser + hADSCs group had a higher resting pressure compared with the sphincterotomy (p < 0.0001), laser (p < 0.0001), and hADSCs (p = 0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p < 0.0001), without a significant difference between treatments (p > 0.05). In the laser + hADSCs group, motor unit numbers were higher than those in the laser group (p < 0.0001) but did not differ from the hADSCs group (p = 0.075). Sphincterotomy increased collagen content, but the muscle content (p = 0.36) and collagen content (p = 0.37) were not significantly different between the laser + hADSCs and control groups. Laser + hADSCs increased ACTA1 (p = 0.001) and MHC (p < 0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p = 0.009) and Ki67 mRNA expression (p = 0.01) and decreased vimentin mRNA expression (p < 0.0001) compared with laser. CONCLUSION: The combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

The Effect of Alpha-Tocopherol on Morphine Tolerance-induced Expression of c-fos Proto-oncogene from a Biotechnological Perspective.

BACKGROUND: The increase of oxidant compounds is the most well-known reasons for the tolerance to the analgesic properties of Morphine. Additionally, the production of proxy-nitrite impairs receptors, proteins and enzymes involved in the signaling pathways of analgesia, apoptosis and necrosis. Also, we revised all patents relating to opioid tolerance control methods. OBJECTIVE: The aim of this study was to assess the effects of Alpha-tocopherol as an anti-oxidant agent to reduce Morphine tolerance. METHOD: Forty male rats randomly divided into four groups. 10 mg/kg of morphine was injected subcutaneously to create the desired level of tolerance. After modeling, 70 mg/kg Alpha- Tocopherol was injected intraperitoneal. Also, the hot plate recorded pain threshold alterations was used to evaluate the behavioral test. All tissue samples were extracted from the spinal cord, thalamus and frontal cortex for molecular and gene expression evaluations. Also, the effect of Alpha- Tocopherol on the apoptosis and necrosis parameters was analyzed using nissl staining and tunel test. RESULTS: The time latency results showed that there were no significant differences in the different days in groups treated with Morphine plus Alpha-Tocopherol. However, our data highlighted that the pain threshold and their time latency in respond to it had substantially increased in comparison with the control group. Furthermore, we found that the Alpha-Tocopherol obviously decreased c-fos gene expression, especially in the spinal cord. CONCLUSION: Thus, co-administration of Alpha-Tocopherol with Morphine can decrease the adverse effects of nitrite proxy, which is released due to repeated injections of Morphine.

Combine effect of Chondroitinase ABC and low level laser (660nm) on spinal cord injury model in adult male rats.

After spinal cord injury (SCI) there are many recoveries inhibiting factors such as chondroitin sulfate proteoglycan (CSPG) and inflammation. The present study investigated the combinational effect of low level laser therapy (LLLT) as anti-inflammatory agent and Chondroitinase ABC (ChABC) enzyme as CSPG digesting factor on spinal cord after injury. This study performed on 44 male Wistar rats, spinal cord injury induced by a clip compression injury. Animals received two-weeks treatment of 660nm low level laser (LLL) and intraspinal injection of 1µg ChABC. Functional recovery, cavity size, myelination, axonal projections around the cavity, fibroblast invasion and expression of glycogen synthase kinase-3ß (GSk 3ß), CSPG and aquaporin 4 (AQP4) expression were evaluated. In statistical evaluation p<0.05 considered significant. Result showed the combination of LLLT and ChABC have more effect on reduction of cavity size, improvement of myelination and number of axons around the cavity and decreasing the expression of GSK3ß, CSPG and AQP4 expression compared to LLLT and ChABC alone. In the laser and laser+enzyme groups AQP4 expression decreased significantly after SCI. Functional recovery, improved in LLLT and ChABC treated animals, but higher recovery belonged to the combination therapy group. The current study showed combination therapy by LLLT and ChABC is more efficient than a single therapy with each of them.

Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury

The present study was designed to elucidate the outcome of subchronic co-administration of black tea and nicotine on cardiovascular performance and whether these substances could modulate the isoproterenol-induced cardiac injury. Animal groups were control, black tea, nicotine and black tea plus nicotine. Test groups received nicotine (2 mg/kg s.c.) and black tea brewed (p.o.) each alone and in combination for 4 weeks. On the 28th day, myocardial damage was induced by isoproterenol (50 mg/kg i.p.), and blood samples were taken. On day 29, after hemodynamic parameters recording, hearts were removed for histopathological evaluation. Tea or nicotine consumption had no significant effects on hemodynamic indices of animals without heart damage. When the cardiac injury was induced, tea consumption maintained the maximum dp/dt, and nicotine significantly decreased the pressure-rate product. Moreover, severity of heart lesions was lower in the presence of nicotine or black tea. Concomitant use of these materials did not show extra effects on mentioned parameters more than the effect of each of them alone. The results suggest that subchronic administration of black tea or nicotine for a period of 4 weeks may have a mild cardioprotective effect, while concomitant use of these materials cannot intensify this beneficial effect (AU)

Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury.

The present study was designed to elucidate the outcome of subchronic co-administration of black tea and nicotine on cardiovascular performance and whether these substances could modulate the isoproterenol-induced cardiac injury. Animal groups were control, black tea, nicotine and black tea plus nicotine. Test groups received nicotine (2 mg/kg s.c.) and black tea brewed (p.o.) each alone and in combination for 4 weeks. On the 28th day, myocardial damage was induced by isoproterenol (50 mg/kg i.p.), and blood samples were taken. On day 29, after hemodynamic parameters recording, hearts were removed for histopathological evaluation. Tea or nicotine consumption had no significant effects on hemodynamic indices of animals without heart damage. When the cardiac injury was induced, tea consumption maintained the maximum dp/dt, and nicotine significantly decreased the pressure-rate product. Moreover, severity of heart lesions was lower in the presence of nicotine or black tea. Concomitant use of these materials did not show extra effects on mentioned parameters more than the effect of each of them alone. The results suggest that subchronic administration of black tea or nicotine for a period of 4 weeks may have a mild cardioprotective effect, while concomitant use of these materials cannot intensify this beneficial effect.