Neuroprotective efficacy of ebselen, an anti‐oxidant with anti‐inflammatory actions, in a rodent model of permanent middle cerebral artery occlusion

Takasago, Teiichi; Peters, E. E.; Graham, David I.; Masayasu, Hiroyuki; Macrae, I. Mhairi

doi:10.1038/sj.bjp.0701426

Cited by 149 publications

(86 citation statements)

References 36 publications

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“…In rodent models of MCA-distribution ischemia, ebselen reduced ischemic damage when administered prior to ischemia (Namura et al, 2001) and was modestly protective if begun 30 min after induction of ischemia (Takasago et al, 1997). When treatment was begun at the onset of recirculation after 2-h MCA occlusion in rats, ebselen reduced early brain injury and improved neurological deficits at 24 hours (Imai et al, 2001), but this protection was not sustained at 7 days (Salom et al, 2004).…”

Section: Other Antioxidants: Tirilazad Ebselen Edaravonementioning

confidence: 99%

Neuroprotection for ischemic stroke: Past, present and future

2008

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Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. Rigorously conducted experimental studies in animal models of brain ischemia provide incontrovertible proof-of-principle that high-grade protection of the ischemic brain is an achievable goal. Nonetheless, many agents have been brought to clinical trial without a sufficiently compelling evidence-based pre-clinical foundation. At this writing, around 160 clinical trials of neuroprotection for ischemic stroke have been initiated. Of the approximately 120 completed trials, two-thirds were smaller early-phase safetyfeasibility studies. The remaining one-third were typically larger (>200 subjects) phase II or III trials, but, disappointingly, only fewer than one-half of these administered neuroprotective therapy within the 4-6 hour therapeutic window within which efficacious neuroprotection is considered to be achievable. This fact alone helps to account for the abundance of "failed" trials.This review presents a close survey of the most extensively evaluated neuroprotective agents and classes and considers both the strengths and weakness of the pre-clinical evidence as well as the results and shortcomings of the clinical trials themselves. Among the agent-classes considered are calcium channel blockers; glutamate antagonists; GABA agonists; antioxidants/radical scavengers; phospholipid precursor; nitric oxide signal-transduction down-regulator; leukocyte inhibitors; hemodilution; and a miscellany of other agents. Among promising ongoing efforts, therapeutic hypothermia, high-dose human albumin therapy, and hyperacute magnesium therapy are considered in detail. The potential of combination therapies is highlighted. Issues of clinical-trial funding, the need for improved translational strategies and clinical-trial design, and "thinking outside the box" are emphasized. Part I: Neuroprotection -from Past to the PresentNeuroprotection for ischemic brain injury has emerged only recently as a topic of serious biomedical inquiry. A MEDLINE survey (PubMed, 2007) reveals virtually no publications on this topic until the early 1990's but a remarkable surge in publications over the past 10 years Correspondence and reprint requests to:

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Section: Other Antioxidants: Tirilazad Ebselen Edaravonementioning

confidence: 99%

Neuroprotection for ischemic stroke: Past, present and future

2008

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“…Most anti-oxidant and anti-inflammatory agents attenuate free radical toxicity (Takasago et al 1997) and have the ability to enhance chondrocyte proliferation and matrix secretion (Shang et al 2009;Wann et al 2010). A series of antioxidants, such as vitamin C (Tiku et al 2003), vitamin E (Bhatti et al 2013), and sodium ferulate (Shang et al 2009), have been demonstrated their chondro-protective properties, as well as potentials in reducing apoptosis and senescence.…”

Section: Introductionmentioning

confidence: 99%

Chondroprotective Effects of Taurine in Primary Cultures of Human Articular Chondrocytes

Liu

et al. 2015

Tohoku J. Exp. Med.

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Articular cartilage is characterized by the lack of blood vessels and has a poor self-healing potential. Limited cell numbers and dedifferentiation of chondrocytes when expanded in vitro are the major obstacles of autologous chondrocyte implantation. Autologous chondrocyte implantation is a cell-based treatment that can be used as a second-line measure to regenerate chondral or osteochondral defects in younger, active patients. There is an urgent need to find an effective chondrogenic protection agent alleviating or inhibiting chondrocyte dedifferentiation. In this study, we explored the effect of taurine (2-aminoethane sulfonic acid) on proliferation and phenotype maintenance of human articular chondrocytes by analyzing the cell proliferation, morphology, viability, and expression of cartilage specific mRNAs and proteins. Primary chondrocytes were isolated from human articular cartilage tissues. Results showed that taurine effectively promoted chondrocyte growth and enhanced accumulation of glycosaminoglycans and collagens in the conditioned media of chondrocytes. Moreover, taurine exposure caused significant increases in the relative expression levels of mRNAs for cartilage specific markers, including aggrecan, collagen type II and SOX9. Aggrecan is a cartilage-specific proteoglycan, and SOX9 is a chondrogenic transcription factor. In contrast, the mRNA expression of collagen type I, a marker for chondrocyte dedifferentiation, was significantly decreased in cells treated with taurine, indicating that taurine inhibits the chondrocyte dedifferentiation. This study reveals that taurine is effective in proliferation promotion and phenotype maintenance of chondrocytes. Thus, taurine may be a useful pro-chondrogenic agent for autologous chondrocyte implantation in the treatment of cartilage repair.

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“…Unlike other selenium compounds, ebselen possesses a very low toxicity because of its unique stability in structure and because its selenium moiety is not liberated during biotransformation and therefore does not enter the selenium metabolism of the organism (7)(8)(9). In more recent animal model studies, ebselen was shown to reduce oxidative stress in ischemiareperfusion in heart (10) and to have neuroprotective effects in brain (11)(12)(13)(14). More importantly, ebselen has been demonstrated to have beneficial effects in clinical trials for the treatment of patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage (15) and acute ischemic stroke (16,17).…”

mentioning

confidence: 99%