ABSTRACT
This is a systematic review and meta-analysis of existing evidence regarding the possible effects of epothilones on spinal cord injury (SCI). This study aimed to investigate the possible effects of epothilone administration on locomotion recovery in animal models of SCI. Despite increasing rates of SCI and its burden on populations, no consensus has been reached about the possible treatment modality for SCI. Meanwhile, low-dose epothilones have been reported to have positive effects on SCI outcomes. Electronic databases of Web of Science, Scopus, Embase, and Medline were searched using keywords related to epothilones and SCI until the end of 2020. Two researchers screened the articles, and extracted data were analyzed using STATA ver. 14.0. Final results are reported as a standardized mean difference (SMD) with a 95% confidence interval (CI). After the screening, five studies were included in the analysis. Rats were used in all the studies. Two types of epothilones were used via intraperitoneal injection and were shown to have positive effects on the motor outcomes of samples with SCI (SMD, 0.87; 95% CI, 0.51 to 1.23; p =0.71). Although a slightly better effect was observed when using epothilone B, the difference was not significant (coefficient, -0.50; 95% CI, -1.52 to 0.52; p =0.246). The results of this study suggest that epothilones have positive effects on the improvement of motor function in rats, when administered intraperitoneally until a maximum of 1 day after SCI. However, current evidence regarding the matter is still scarce.
ABSTRACT
Background: Considering the limitations of cell therapy, in case of adequate treatment efficacy, conditioned media (CM) may be a desirable alternative to cell therapy. Hence, the present systematic review and meta-analysis aims to evaluate the efficacy of mesenchymal stem cell-derived conditioned media (MSC-CM) in movement resolution following spinal cord injury (SCI) in animal models. Methods: A comprehensive search in the databases of Medline, Scopus, Web of Science, and Embase was completed until the end of March 2021. Animal studies that evaluate the efficacy of MSC-CM on movement resolution following SCI were defined as the inclusion criteria. Lack of an SCI-untreated group, CM derived from a source other than MSC, not assessing motor function, failure to report CM administered dose, a follow-up period of less than 4 weeks, duplicates, and review articles were counted as the exclusion criteria. Final results are presented as overall standardized mean difference (SMD) with a 95% confidence interval (CI). Results: From the 361 nonduplicate articles, data from 11 articles were entered into the present meta-analysis. The analyses showed that MSC-CM administration in SCI animal models promotes motor recovery (SMD=2.32; 95% CI: 1.55, 3.09; p<0.0001). Subgroup analysis was performed because of the noticeable heterogeneity between the studies (I2=80.97%, p<0.0001), depicting that antibiotic administration, delivery amount, delivery type, and follow-up time were the possible sources of heterogeneity. Moreover, multiple meta-regression demonstrated that in cases of delivery amount of more than 120 µL, the efficacy of MSC-CM administration in motor recovery is more than that of delivery amount of less than 120 µL (regression coefficient=3.30; 95% CI: 0.72, 5.89; p=0.019). Conclusions: Based on the results of the present study, it can be concluded that MSC-CM administration in SCI models improves motor recovery. The efficacy of this treatment strategy significantly increases at doses higher than 120 µL.
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BACKGROUND: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. METHODS: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). RESULTS: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia. CONCLUSIONS: A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.
ABSTRACT
BACKGROUND: As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. METHODS: The search strategy was developed based on keywords related to 'spinal cord injury' and 'extracorporeal shockwave therapy'. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. RESULTS: Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05-2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 (P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). CONCLUSION: Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.
Subject(s)
Extracorporeal Shockwave Therapy , Spinal Cord Injuries , Animals , Spinal Cord Injuries/therapy , Vascular Endothelial Growth Factor AABSTRACT
CONTEXT: The present systematic review and meta-analysis aims to perform an extensive search in databases to compare the efficacy of the intranasal administration of naloxone with its intramuscular/intravenous administration in the pre-hospital management of opioid overdose. EVIDENCE ACQUISITION: This meta-analysis included controlled trials conducted on the efficacy of naloxone administration in the pre-hospital management of opioid overdose. A search was carried out in electronic databases on relevant articles published by the end of 2018. After data collection, analyses were performed in STATA 14.0 software and the efficacy and side-effects of the two administration routes of naloxone, i.e. intranasal and intramuscular/intravenous, were compared. An overall effect size with 95% confidence interval (95% CI) was provided for each section. RESULTS: Eventually, data from six studies were included in this meta-analysis. The success rate of the intranasal and intramuscular/intravenous administration of naloxone in the management of opioid overdose in pre-hospital settings was 82.54% (95% CI: 57.97 to 97.89%) and 80.39% (95% CI: 57.38 to 96.04%), respectively. There was no difference between injectable (intramuscular/intravenous) naloxone and intranasal naloxone in the pre-hospital management of opioid overdose (Odds Ratio=1.01; 95% CI: 0.42 to 2.43; P=0.98). The onset of action of intranasal naloxone, however, was slightly longer than injectable naloxone (Standardized Mean Difference=0.63; 95% CI: 0.07 to 1.19; P=0.03). Additionally, the odds of needing a rescue dose was 2.17 times higher for intranasal naloxone than intramuscular/intravenous naloxone (OR=2.17; 95% CI: 1.53 to 3.09; P<0.0001). The prevalence of major side-effects was non-significant for both intranasal (0.00%) and intramuscular/intravenous (0.05%) routes of naloxone administration and there was no difference in the prevalence of major (OR=1.18; 95% CI: 0.38 to 3.69; P=0.777) and minor (OR=0.64; 95% CI: 0.17 to 2.34; P=0.497) side-effects between the two routes. CONCLUSION: The present meta-analysis demonstrated that intranasal naloxone is as effective as injectable naloxone in the pre-hospital management of opioid overdose complications. Consequently, intranasal naloxone may be an appropriate alternative to injectable naloxone.
