scholarly journals Efficacy of Melatonin in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Stratified Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Hu ◽  
Yuwei Zhu ◽  
Fangfang Zhou ◽  
Cuiying Peng ◽  
Zhiping Hu ◽  
...  

Background and Purpose: Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH.Methods: The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD).Results: Our literature identified 160 possible articles, and most of them were excluded due to duplication (n = 69) and failure to meet the inclusion criteria (n = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures (n = 16), no relevant interventions (n = 3), review articles (n = 1), duplicated publications (n = 1), and studies on humans or cells (n = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models.Conclusion: Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.

2012 ◽  
Vol 32 (9) ◽  
pp. 1645-1658 ◽  
Author(s):  
Tommaso Zoerle ◽  
Don C Ilodigwe ◽  
Hoyee Wan ◽  
Katarina Lakovic ◽  
Mohammed Sabri ◽  
...  

Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of −1.74; 95% confidence interval −2.04 to −1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm >3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm >3 days after SAH may be preferable for preclinical models.


2020 ◽  
Vol 2020 ◽  
pp. 1-21 ◽  
Author(s):  
Fei-Yi Zhao ◽  
Qiang-Qiang Fu ◽  
Zhen Zheng ◽  
Li-Xing Lao ◽  
Hua-Ling Song ◽  
...  

Background. Alzheimer’s disease (AD) is a common health condition affecting senile people and leads to severe cognitive dysfunctions. Acupuncture has been shown to be a possible alternative natural remedy for AD in some animal studies. Objective. To perform a systematic review to identify the effect of verum-acupuncture compared with sham-acupuncture on learning and memory performance among animal models of AD. Methods. Experimental animal studies of treating AD via verum- and sham- acupuncture were searched in nine electronic databases, including Sciverse ScienceDirect, PubMed, Springer, Ebsco Medline, AMED, EMBASE (Elsevier), Scopus (Elsevier), PsycINFO (ProQuest), and OVID from the dates of the databases’ inception to June 2019. The Morris water maze test was considered as an outcome measure. The software Revman 5.3 and Stata 16.0 were used to conduct the meta-analysis. Heterogeneity was examined by using I2 statistics. The publication bias was assessed via Begg’s test by Stata 16.0. Results. Twelve studies involving 229 animals met the inclusion criteria. Most of the studies had a moderate quality according to SYRCLE's risk of bias tool for animal studies. The results of the meta-analysis indicated that verum-acupuncture could reduce the escape latency (MD = −12.90, 95% CI (−17.08, −8.71), p<0.001) and increase the time spent in the original platform quadrant (MD = 7.28, 95% CI (4.23, 10.33), p<0.001) and frequency of the crossing former platform (MD = 2.01, 95% CI (1.53, 2.50), p<0.001) compared with the sham-acupuncture. Conclusions. Acupuncture is effective in improving cognitive functions in AD animal models, and this benefit is more than just a placebo effect. Further clinical trials are needed to confirm the findings.


2015 ◽  
Vol 35 (7) ◽  
pp. 1085-1089 ◽  
Author(s):  
Kamil G Laban ◽  
Mervyn DI Vergouwen ◽  
Rick M Dijkhuizen ◽  
Emily S Sena ◽  
Malcolm R Macleod ◽  
...  

In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wanying Xu ◽  
Dominique Pepper ◽  
Junfeng Sun ◽  
Judith Welsh ◽  
Xizhong Cui ◽  
...  

Background. Clinical studies suggest obesity paradoxically increases survival during bacterial infection and sepsis but decreases it with influenza, but these studies are observational. By contrast, animal studies of obesity in infection can prospectively compare obese versus nonobese controls. We performed a systematic review and meta-analysis of animal investigations to further examine obesity’s survival effect in infection and sepsis. Methods. Databases were searched for studies comparing survival in obese versus nonobese animals following bacteria, lipopolysaccharide, or influenza virus challenges. Results. Twenty-one studies (761 obese and 603 control animals) met the inclusion criteria. Obesity reduced survival in 19 studies (11 significantly) and the odds ratio (95% CI) of survival (0.21(0.13, 0.35); I2 = 64%, p<0.01p < 0.01) but with high heterogeneity. Obesity reduced survival (1) consistently in both single-strain bacteria- and lipopolysaccharide-challenged studies (n = 6 studies, 0.21(0.13, 0.34); I2 = 31%, p=0.20 and n = 5, 0.22(0.13, 0.36); I2 = 0%, p=0.59, respectively), (2) not significantly with cecal ligation and puncture (n = 4, 0.72(0.08, 6.23); I2 = 75%, p<0.01), and (3) significantly with influenza but with high heterogeneity (n = 6, 0.12(0.04, 0.34); I2 = 73%, p<0.01). Obesity’s survival effects did not differ significantly comparing the four challenge types (p=0.49). Animal models did not include antimicrobials or glycemic control and study quality was low. Conclusions. Preclinical and clinical studies together emphasize the need for prospective studies in patients accurately assessing obesity’s impact on survival during severe infection.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chema Strik ◽  
Kimberley E. Wever ◽  
Martijn W. J. Stommel ◽  
Harry van Goor ◽  
Richard P. G. ten Broek

AbstractToday, 40–66% of elective procedures in general surgery are reoperations. During reoperations, the need for adhesiolysis results in increased operative time and a more complicated convalescence. In pre-clinical evaluation, adhesion barriers are tested for their efficacy in preventing ‘de novo’ adhesion formation, However, it is unknown to which extent barriers are tested for prevention of adhesion reformation. The aim of this systematic review and meta-analysis is to assess the efficacy of commercially available adhesion barriers and laparoscopic adhesiolysis in preventing adhesion reformation in animal models. Pubmed and EMBASE were searched for studies which assessed peritoneal adhesion reformation after a standardized peritoneal injury (in the absence of an intra-peritoneal mesh), and reported the incidence of adhesions, or an adhesion score as outcome. Ninety-three studies were included. No study met the criteria for low risk of bias. None of the commercially available adhesion barriers significantly reduced the incidence of adhesion reformation. Three commercially available adhesion barriers reduced the adhesion score of reformed adhesions, namely Seprafilm (SMD 1.38[95% CI]; p < 0.01), PEG (SMD 2.08[95% CI]; p < 0.01) and Icodextrin (SMD 1.85[95% CI]; p < 0.01). There was no difference between laparoscopic or open adhesiolysis with regard to the incidence of adhesion reformation (RR 1.14[95% CI]; p ≥ 0.05) or the adhesion score (SMD 0.92[95% CI]; p ≥ 0.05). Neither currently commercially available adhesion barriers, nor laparoscopic adhesiolysis without using an adhesion barrier, reduces the incidence of adhesion reformation in animal models. The methodological quality of animal studies is poor.


2020 ◽  
Vol 11 (6) ◽  
pp. 1175-1184 ◽  
Author(s):  
Basil E. Grüter ◽  
Davide Croci ◽  
Salome Schöpf ◽  
Edin Nevzati ◽  
Donato d’Allonzo ◽  
...  

2021 ◽  
pp. postgradmedj-2021-139939
Author(s):  
Xiaohui Liu ◽  
Hongwei Wang ◽  
Si Shi ◽  
Jinling Xiao

BackgroundSo far, SARS-CoV-2 is the seventh coronavirus found to infect humans and cause disease with quite a strong infectivity. Patients diagnosed as severe or critical cases are prone to multiple organ dysfunction syndrome, acute respiratory distress syndrome and even death. Proinflammatory cytokine IL-6 has been reported to be associated with the severity of disease and mortality in patients with COVID-19.ObjectiveThis systematic review and meta-analysis were carried out to evaluate the association between IL-6 and severe disease and mortality in COVID-19 disease.MethodsA systematic literature search using China National Knowledge Infrastructure, Wanfang databases, China Science and Technology Journal Database, Chinese Biomedical Literature, Embase, PubMed and Cochrane Central Register of Controlled Trials was performed from inception until 16 January 2021.Results12 studies reported the value of IL-6 for predicting the severe disease in patients with COVID-19. The pooled area under the curve (AUC) was 0.85 (95% CI 0.821 to 0.931). 5 studies elaborated the predictive value of IL-6 on mortality. The pooled sensitivity, specificity and AUC were 0.15 (95% CI 0.13 to 0.17, I2=98.9%), 0.73 (95% CI 0.65 to 0.79, I2=91.8%) and 0.531 (95% CI 0.451 to 0.612), respectively. Meta-regression analysis showed that country, technique used, cut-off, sample, study design and detection time did not contribute to the heterogeneity of mortality.ConclusionIL-6 is an adequate predictor of severe disease in patients infected with the COVID-19. The finding of current study may guide clinicians and healthcare providers in identifying potentially severe or critical patients with COVID-19 at the initial stage of the disease. Moreover, we found that only monitoring IL-6 levels does not seem to predict mortality and was not associated with COVID-19’s mortality.PROSPERO registration numberCRD42021233649.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Haider Al-Waeli ◽  
Ana Paula Reboucas ◽  
Alaa Mansour ◽  
Martin Morris ◽  
Faleh Tamimi ◽  
...  

Abstract Background Non-steroidal anti-inflammatory drugs (NSAID) have excellent anti-inflammatory and analgesic properties and are extensively used to treat post-traumatic or surgical musculoskeletal pain. Although an extensive literature exists on the administration of NSAID on animal bone healing, no systematic review and meta-analysis of animal studies that investigate the effect of NSAID administration on bone fracture healing. Objective of this study is to conduct a systematic review and meta-analysis to estimate the effect of NSAIDs administration on bone healing biomechanical and histomorphometric measurements in different animal models after bone fracture surgery. Methods We performed a systematic review and meta-analysis of animal studies to estimate the effect of NSAID administration after bone fracture on healing outcomes. We searched eight databases without limiting the search to starting date up to 1 February 2021 for articles on fractured bone healing in animal models in which NSAID were administered. Results Out of 6732 articles screened, 47 were included and 3 common bone healing outcomes were analysed: biomechanical properties (maximum force to break, stiffness, and work-to-failure), micro-computed tomography (μ-CT), and histomorphometric measurements. The studies were generally of low-quality scores because crucial information, especially concerning randomization, blinding, and allocation concealment, was poorly reported. Our results show that the negative effects of NSAID after bone fracture on certain biomechanical properties of the healing bones was not statistically significant in mice compared with other animals, in females compared with males, and in younger compared with older animals. Conclusion The findings demonstrated that NSAIDs administration decreased the biomechanical properties of healing bones after fracture surgery in comparison to the control group. Moreover, different effect on certain outcomes was detected among different sites, sex of the animals, and the time of assessment. Trial registration Protocol published and registered in SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) in 2017, https://www.radboudumc.nl/getmedia/757ec408-7a9e-4635-8233-ae951effea54/Non-Steroidal-Anti-inflammatory-Drugs-and-bone-healing-in-animal-Models-Systematic-Review-and-Meta-Analysis.aspx


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