Combined and individual use of pancaspase inhibitor Q-VD-OPh and NMDA receptor antagonist Riluzole in experimental spinal cord injury

Can, Halil

doi:10.5505/tjtes.2017.09694

Cited by 6 publications

(14 citation statements)

References 42 publications

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“…; Can et al . ; Martins et al . ), while the remaining publications caused injury to the C5–T1 levels.…”

Section: Resultsmentioning

confidence: 99%

“…Of the 19 publications excluded at the full-text level, nine did not report an outcome that met the inclusion criteria (Stutzmann et al 1996;Springer et al 1997;Zhang 1999;Lang-Lazdunski et al 2000;Mu et al 2000a;Hachem et al 2015;Sarkar et al 2016;Satkunendrarajah et al 2016;Shimizu et al 2018), three used a global ischemia or transection model of SCI (Kitzman 2009;Wu et al 2014;Caglar et al 2018), one study close to the inclusion criteria caused disagreement, but was excluded due to use of the chronic model of SCI after discussion with the third reviewer (Hama and Sagen 2011), one combined riluzole with another treatment (Dulin et al 2013), the data of three conference proceedings (Wu 2009;Wu et al 2010;Satkunendrarajah et al 2013) were part of Wu et al (2013Wu et al ( , 2014 respectively, one conference proceeding (Sarkar et al 2017) and Sarkar et al (2016) were the same study, and the data of the remaining article (Zhang et al 2001) was part of Zhang (1999). A total of 10 studies were included in this systematic review and meta-analysis ( Figure 1; Mu et al 2000b;Schwartz and Fehlings 2001;Ates et al 2007;Satkunendrarajah and Fehlings 2012;Simard et al 2012;Wu et al 2013;Hosier et al 2015;Vasconcelos et al 2016;Can et al 2017;Martins et al 2018).…”

Section: Study Selectionmentioning

confidence: 99%

“…The sample size ranged from 19 to 90 animals. Five studies induced SCI using a weight-drop impactor (Mu et al 2000b;Ates et al 2007;Simard et al 2012;Hosier et al 2015;Vasconcelos et al 2016), and the remaining studies used an aneurysm clip compression method (Schwartz and Fehlings 2001;Satkunendrarajah and Fehlings 2012;Wu et al 2013;Can et al 2017;Martins et al 2018). Five studies reported trauma at the T7-T12 levels (Mu et al 2000b;Ates et al 2007;Vasconcelos et al 2016;Can et al 2017;Martins et al 2018), while the remaining publications caused injury to the C5-T1 levels.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

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Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta‐analysis and systematic review

Zhou

Tian

Yao

et al. 2019

Journal of Neurochemistry

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Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. PubMed, Embase, Cochrane Library, and Chinese databases were searched from their inception date to March 2018. Two reviewers independently selected animal studies that evaluated neurological recovery and lesion area following riluzole treatment in SCI rat models, extracted data and assessed methodological quality. Pairwise meta‐analysis, subgroup analysis, and network meta‐analysis were performed to assess the effects of riluzole on SCI. Ten eligible studies were included. Two studies had high methodological quality. Overall, the Basso, Beattie, and Bresnahan scores were increased in riluzole‐treated animals versus controls, and effect sizes showed a gradual increase from the 1st (five studies, n = 104, mean difference = 1.24, 95% CI = 0.11 to 2.37, p = 0.03) to 6th week after treatment (five studies, n = 120, mean difference = 2.34, 95% CI = 1.26 to 3.42, p < 0.0001). Riluzole was associated with improved outcomes in the inclined plane test and the tissue preservation area. Subgroup analyses suggested an association of locomotor recovery with riluzole dose. Network meta‐analysis showed that 5 mg/kg riluzole exhibited greater protection than 2.5 and 8 mg/kg riluzole. Collectively, this review suggests that riluzole has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials or applications. However, animal results should be interpreted with caution given the known limitations in animal experimental design and methodological quality.

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“…; Can et al . ; Martins et al . ), while the remaining publications caused injury to the C5–T1 levels.…”

Section: Resultsmentioning

confidence: 99%

Section: Study Selectionmentioning

confidence: 99%

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta‐analysis and systematic review

Zhou

Tian

Yao

et al. 2019

Journal of Neurochemistry

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“…Histopathological experiments have shown that after SCI, riluzole increased rostrocaudal and epicenter tissue sparing with decreased lesion volume, increased axonal sparing, and increased serotonergic fibers. 38,48,55 Other studies have shown an increase in glial cell and neuronal survival, 6,34,44,58 decrease in reactive oxygen species, 49 increase in synaptophysin expression in the ventral horn, 47 decrease in capillary fragmentation, 50 decrease in pyknosis and hypoplasia of ventral motor neurons, 49 decrease in lymphocytes and granulocytes, 7 increase in choline acetylcholine transferase staining in motor neurons, 21 decrease in lactate dehydrogenase, 23 decrease in TUNEL staining apoptotic neurons, 32,58,57 decrease in macrophages and microglia, 58 and decrease in lipid peroxidation and water content. 1 Electrophysiological experiments have suggested a decrease in muscle spasm, 5 attenuation of altered reflex mechanisms, 47 and increase in amplitude of somatosensory evoked potentials.…”

Section: Animal Studiesmentioning

confidence: 99%

Efficacy of riluzole in the treatment of spinal cord injury: a systematic review of the literature

Srinivas¹,

Wali²,

Pham³

2019

Neurosurgical Focus

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OBJECTIVERiluzole is a glutamatergic modulator that has recently shown potential for neuroprotection after spinal cord injury (SCI). While the effects of riluzole are extensively documented in animal models of SCI, there remains heterogeneity in findings. Moreover, there is a paucity of data on the pharmacology of riluzole and its effects in humans. For the present study, the authors systematically reviewed the literature to provide a comprehensive understanding of the effects of riluzole in SCI.METHODSThe PubMed database was queried from 1996 to September 2018 to identify animal studies and clinical trials involving riluzole administration for SCI. Once articles were identified, they were processed for year of publication, study design, subject type, injury model, number of subjects in experimental and control groups, dose, timing/route of administration, and outcomes.RESULTSA total of 37 studies were included in this study. Three placebo-controlled clinical trials were included with a total of 73 patients with a mean age of 39.1 years (range 18–70 years). For the clinical trials included within this study, the American Spinal Injury Association Impairment Scale distributions for SCI were 42.6% grade A, 25% grade B, 26.6% grade C, and 6.2% grade D. Key findings from studies in humans included decreased nociception, improved motor function, and attenuated spastic reflexes. Twenty-six animal studies (24 in vivo, 1 in vitro, and 1 including both in vivo and in vitro) were included. A total of 520 animals/in vitro specimens were exposed to riluzole and 515 animals/in vitro specimens underwent other treatment for comparison. The average dose of riluzole for intraperitoneal, in vivo studies was 6.5 mg/kg (range 1–10 mg/kg). Key findings from animal studies included behavioral improvement, histopathological tissue sparing, and modified electrophysiology after SCI. Eight studies examined the pharmacology of riluzole in SCI. Key findings from pharmacological studies included riluzole dose-dependent effects on glutamate uptake and its modified bioavailability after SCI in both animal and clinical models.CONCLUSIONSSCI has many negative sequelae requiring neuroprotective intervention. While still relatively new in its applications for SCI, both animal and human studies demonstrate riluzole to be a promising pharmacological intervention to attenuate the devastating effects of this condition.

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“…The experimental SCI model was established as described previously (Soubeyrand et al, 2014;Can et al, 2017) and we selected two of three groups randomly undergoing the SCI surgery. Briefly, general anesthesia was achieved by administration of 5% isoflurane and maintenance by 1.5% isoflurane.…”

Section: Sci Modelmentioning

confidence: 99%

Treatment With 2-BFI Attenuated Spinal Cord Injury by Inhibiting Oxidative Stress and Neuronal Apoptosis via the Nrf2 Signaling Pathway

Lin

Zhu

et al. 2019

Front. Cell. Neurosci.

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Previous reports showed that 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) has antioxidant, anti-inflammatory and anti-apoptotic effects on neuroprotection in numerous disorders. However, the precise mechanisms remain elusive. The nuclear factor c factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an important and essential role in the antioxidant and anti-inflammatory responses of the cell. Therefore, the purpose of this study was to investigate the potential neuroprotective effects of 2-BFI in a rat model of spinal cord injury (SCI) and to determine whether its neuroprotective effects are associated with the activation of Nrf2. To test this hypothesis, we examined the potential roles of 2-BFI in SCI models which were established in rats using a clip-compression injury method. Our results showed that treatment with 2-BFI twice daily improved locomotion recovery from SCI, which increased Nrf2 expression in both neurons and astrocytes, meanwhile, the level of heme oxygenase-1 (HO-1) also significantly enhanced. In addition, after the treatment with 2-BFI increased levels of superoxidase dismutase (SOD) and glutathione peroxidase (GPx) indicated the antioxidant effect of the drug. Furthermore, the upregulation of Bcl-2 and downregulation of Bax and caspase-3 implied antiapoptotic effects on neuroprotection of 2-BFI, which were verified by the Fluoro-Jade B (FJB) staining and TUNEL staining. Collectively, these results add to a growing body of evidence supporting that 2-BFI may attenuate SCI mediated by activation of the Nrf2/HO-1 signaling pathway.

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Combined and individual use of pancaspase inhibitor Q-VD-OPh and NMDA receptor antagonist Riluzole in experimental spinal cord injury

Abstract: BACKGROUND:We investigated the effects of an N-methyl-D-aspartate receptor antagonist, riluzole, and a pancaspase inhibitor and basic apoptosis mediator, Q-VD-OPh, in combination or alone in posttraumatic spinal cord injury.

Cited by 6 publications

References 42 publications

Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta‐analysis and systematic review

Riluzole promotes neurological function recovery and inhibits damage extension in rats following spinal cord injury: a meta‐analysis and systematic review

Efficacy of riluzole in the treatment of spinal cord injury: a systematic review of the literature

Treatment With 2-BFI Attenuated Spinal Cord Injury by Inhibiting Oxidative Stress and Neuronal Apoptosis via the Nrf2 Signaling Pathway

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