Neuroprotective effect and possible mechanism of edaravone in rat models of spinal cord injury: a protocol for a systematic review and meta-analysis
Tóm tắt
Spinal cord injury (SCI) is one of the most disabling neurological conditions, afflicting thousands of human beings. Edaravone, a well-known reactive oxygen species scavenger, is expanding its new scope in field of SCI. The objective of this systematic review is to determine the neuroprotective effects and discuss the underlying mechanism of edaravone in management of SCI. The systematic review will include the controlled studies evaluating the neurological roles of edaravone on experiment rat models following SCI. The primary outcome will be the 21-point Basso, Beattie, and Bresnahan locomotor rating scale. The secondary outcomes will include the preservation of white matter areas and malondialdehyde levels. Two researchers will independently search PubMed, Embase, Web of Science, Scopus and Cochrane Library from their inception date. Following study selection, data extraction, and assessment of methodological quality in included studies using the SYRCLE’s RoB tool, data from eligible studies will be pooled and analyzed using random-effects models with RevMan 5.3 software. In case of sufficient data, subgroup analyses with respect to species, age, gender, injury characteristics, or administration details will be carried out to explore the factors modifying efficacy of edaravone. For exploring the appropriate dose of edaravone, a network meta-analysis approach will be conducted based on the Bayesian method. Importantly, the proposed mechanisms and changes of related molecules will be also extracted from included studies for comprehensively investigating the mechanisms underlying the neuroprotective effects of edaravone. In this study, we aim to quantitatively analyze the role of edaravone in locomotor recovery and tissue damage in SCI rat model. The efficacy of edaravone in distinct scenarios will be investigated by subgroup analyses, and we expect to predict the candidate dose that offers a superior treatment effect using network meta-analyses. Moreover, a comprehensive framework regarding the neuroprotective mechanisms behind edaravone will be constructed via a combination of systematic and traditional review. This study will bring implications for future preclinical studies and clinical applications of SCI. Nonetheless, in light of the anticipated limitations in animal experimental design and methodological quality, the results in this review should be interpreted with caution.
Tài liệu tham khảo
Velstra IM, Curt A, Frotzler A, Abel R, Kalsi-Ryan S, Rietman JS, et al. Changes in strength, sensation, and prehension in acute cervical spinal cord injury: European multicenter responsiveness study of the GRASSP. Neurorehabil Neural Repair. 2015;29(8):755–66.
van Den Hauwe L, Sundgren PC, Flanders AE. Spinal trauma and spinal cord injury (sci). Diseases of the Brain, Head and Neck, Spine 2020-2023: Diagnostic Imaging. 2020. p. 231–240.
DeVivo MJ, Chen Y, Wen H. Cause of death trends among persons with spinal cord injury in the United States: 1960–2017. Arch Phys Med Rehabil. 2022;103(4):634–41.
GBD. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(1):56–87.
Quadri SA, Farooqui M, Ikram A, Zafar A, Khan MA, Suriya SS, et al. Recent update on basic mechanisms of spinal cord injury. Neurosurg Rev. 2020;43(2):425–41.
Rabchevsky AG, Michael FM, Patel SP. Mitochondria focused neurotherapeutics for spinal cord injury. Exp Neurol. 2020;330: 113332.
Slater PG, Dominguez-Romero ME, Villarreal M, Eisner V, Larrain J. Mitochondrial function in spinal cord injury and regeneration. Cell Mol Life Sci. 2022;79(5):239.
Siniscalco D, Fuccio C, Giordano C, Ferraraccio F, Palazzo E, Luongo L, et al. Role of reactive oxygen species and spinal cord apoptotic genes in the development of neuropathic pain. Pharmacol Res. 2007;55(2):158–66.
Ahuja CS, Nori S, Tetreault L, Wilson J, Kwon B, Harrop J, et al. Traumatic spinal cord Injury-Repair and regeneration. Neurosurgery. 2017;80(3S):S9–22.
Hall ED. Antioxidant therapies for acute spinal cord injury. Neurotherapeutics. 2011;8(2):152–67.
Okamura K, Tsubokawa T, Johshita H, Miyazaki H, Shiokawa Y. Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia. Neurol Res. 2014;36(1):65–9.
Genge A, Brooks BR, Oskarsson B, Kalin A, Ji M, Apple S, et al. Analysis of the US safety data for edaravone (Radicava((R))) from the third year after launch. Drugs R D. 2022;22(3):205–11.
Kikuchi K, Tancharoen S, Takeshige N, Yoshitomi M, Morioka M, Murai Y, et al. The efficacy of edaravone (radicut), a free radical scavenger, for cardiovascular disease. Int J Mol Sci. 2013;14(7):13909–30.
Hassan MQ, Akhtar MS, Afzal O, Hussain I, Akhtar M, Haque SE, et al. Edaravone and benidipine protect myocardial damage by regulating mitochondrial stress, apoptosis signalling and cardiac biomarkers against doxorubicin-induced cardiotoxicity. Clin Exp Hypertens. 2020;42(5):381–92.
Silva D, Rocha R, Correia AS, Mota B, Madeira MD, Vale N, et al. Repurposed edaravone, metformin, and perampanel as a potential treatment for Hypoxia-Ischemia encephalopathy: An in vitro study. Biomedicines. 2022;10(12):3043.
Singh S, Gautam U, Manvi FV. Protective impact of edaravone against ZnO NPs-induced oxidative stress in the human neuroblastoma SH-SY5Y cell line. Cell Mol Neurobiol. 2022;42(4):1189–210.
Ohta S, Iwashita Y, Takada H, Kuno S, Nakamura T. Neuroprotection and enhanced recovery with edaravone after acute spinal cord injury in rats. Spine. 2005;30(10):1154–8.
Ren X, Yang Y, Jiao J. The neuroprotection effect of edaravone on spinal cord injury in rats. Chinese J Rehabil Med. 2006;21(8):686–8.
Ohta S, Iwashita Y, Kakinoki R, Noguchi T, Nakamura T. Effects of continuous intravenous infusion of MCI-186 on functional recovery after spinal cord injury in rats. J Neurotraum. 2011;28(2):289–98.
Ozgiray E, Serarslan Y, Ozturk OH, Altas M, Aras M, Sogut S, et al. Protective effects of edaravone on experimental spinal cord injury in rats. Pediatr Neurosurg. 2011;47(4):254–60.
Wang J, Guo G, Wang W, Tang Y, Shun J, Zhou X, et al. Effect of Methylprednisolone and Edaravone administration on spinal cord injury. Eur Rev Med Pharmaco. 2013;17(20):2766–72.
Zhao ZJ, Sun ZM, Zhang CY, Han JG, Shi RC, Wang WZ. Edaravone combined with neural stem cell transplantation for treatment of spinal cord injury in rats. Chinese J Tissue Eng Res. 2013;17(10):1862–7.
Ishii H, Petrenko AB, Sasaki M, Satoh Y, Kamiya Y, Tobita T, et al. Free radical scavenger edaravone produces robust neuroprotection in a rat model of spinal cord injury. Brain Res. 2018;1682:24–35.
Li RB, Yu GS, Lin YB, Zhou JF, Huang YQ, Zheng W. Edaravone effects on the expression levels of collagen type i and iv after spinal cord injury in rats. Chinese J Tissue Eng Res. 2018;22(8):1235–40.
Pang Y, Liu X, Wang X, Shi X, Ma L, Zhang Y, et al. Edaravone modulates neuronal GPX4/ACSL4/5-LOX to promote recovery after spinal cord injury. Front Cell Dev Biol. 2022;10: 849854.
Zhou L, Chen X, Yu B, Pan M, Fang L, Li J, et al. The effect of metformin on ameliorating neurological function deficits and tissue damage in rats following spinal cord injury: A systematic review and network meta-analysis. Front Neurosci-Switz. 2022;16: 946879.
Yao M, Yang L, Wang J, Sun Y, Dun R, Wang Y, et al. Neurological recovery and antioxidant effects of curcumin for spinal cord injury in the rat: a network meta-analysis and systematic review. J Neurotraum. 2015;32(6):381–91.
Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1–21.
Ek CJ, Habgood MD, Callaway JK, Dennis R, Dziegielewska KM, Johansson PA, et al. Spatio-temporal progression of grey and white matter damage following contusion injury in rat spinal cord. PLoS ONE. 2010;5(8): e12021.
Balci M, Namuslu M, Devrim E, Durak I. Effects of computer monitor-emitted radiation on oxidant/antioxidant balance in cornea and lens from rats. Mol Vis. 2009;15:2521–5.
Zhou A, Zhu K, Pu P, Li Z, Zhang Y, Shu B, et al. Neuroprotective effect and possible mechanisms of Ginsenoside-Rd for cerebral Ischemia/Reperfusion damage in experimental animal: A Meta-Analysis and systematic review. Oxid Med Cell Longev. 2022;2022:1–16.
Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. Bmc Med Res Methodol. 2014;14:43.
Tian ZR, Yao M, Zhou LY, Song YJ, Ye J, Wang YJ, et al. Effect of docosahexaenoic acid on the recovery of motor function in rats with spinal cord injury: A meta-analysis. Neural Regen Res. 2020;15(3):537–47.
Ashammakhi N, Kim HJ, Ehsanipour A, Bierman RD, Kaarela O, Xue C, et al. Regenerative therapies for spinal cord injury. Tissue Eng Part B Rev. 2019;25(6):471–91.
Timotius IK, Bieler L, Couillard-Despres S, Sandner B, Garcia-Ovejero D, Labombarda F, et al. Combination of defined CatWalk gait parameters for predictive locomotion recovery in experimental spinal cord injury rat models. eNeuro. 2021;8(2):ENEURO.0497–20.