Attenuation of axonal injury and oxidative stress by edaravone protects against cognitive impairments after traumatic brain injury

Ohta, Manabu; Higashi, Youichirou; Yawata, Toshio; Kitahara, Masahiro; Nobumoto, Atsuya; Ishida, Eri; Tsuda, Masayuki; Fujimoto, Yasunori; Shimizu, Katsuji

doi:10.1016/j.brainres.2012.09.011

Cited by 43 publications

(30 citation statements)

References 42 publications

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“…It has been used clinically to reduce neuronal damage resulting from cerebral ischemic stroke in Japan and China (Nakamura et al 2008). In addition, edaravone has displayed its protective effects in a variety of brain diseases, including traumatic brain injury (Ohta et al 2013), Alzheimer's disease (Yan et al 2012), and Parkinson's disease (Yuan et al 2008). Previous research has shown that edaravone plays an important role as a direct and indirect free radical scavenger by neutralizing toxic ROS and reactive nitrogen species (RNS) (Roh et al 2011).…”

mentioning

confidence: 99%

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Chen

Liu

Dong

et al. 2015

Cell Stress and Chaperones

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Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p<0.05). Thus, the current study indicates that edaravone offers protection from radiation-induced cytogenetic alterations.

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mentioning

confidence: 99%

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Chen

Liu

Dong

et al. 2015

Cell Stress and Chaperones

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“…With treatment 1 h after impact, axonal injury was also significantly suppressed and this therapeutic effect persisted up to 6 h after impact. Edaravone therapy protects against memory deficits following TBI mediated by suppression of traumatic axonal injury and oxidative stress (13).…”

Section: Edaravonementioning

confidence: 99%

“…Various mechanisms are postulated to promote free radical production, including glutamate release, intracelular calcium overload, increase in arachidonic acid and its metabolites, hemoglobin denaturation, and iron ion release (1). The production of free radicals evoked by brain injury plays a crucial role in the initiating and propagating the pathogenesis of post-traumatic secondary injury, through oxidation and nitration of the cellular membrane, proteins, and DNA (3,(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant therapies in traumatic brain injury: a review

Romero-Rivera¹,

Cabeza-Morales²,

Soto-Zarate³

et al. 2017

Romanian Neurosurgery

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Abstract:Oxidative stress constitute one of the commonest mechanism of the secondary injury contributing to neuronal death in traumatic brain injury cases. The oxidative stress induced secondary injury blockade may be considered as to be a good alternative to improve the outcome of traumatic brain injury (TBI) treatment. Due to absence of definitive therapy of traumatic brain injury has forced researcher to utilize unconventional therapies and its roles investigated in the improvement of management and outcome in recent year. Antioxidant therapies are proven effective in many preclinical studies and encouraging results and the role of antioxidant mediaction may act as further advancement in the traumatic brain injury management it may represent aonr of newer moadlaity in neurosurgical aramamentorium, this kind of therapy could be a good alternative or adjuct to the previously established neuroprotection agents in TBI.

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“…One study has shown that treating with Edaravone, a free radical scavenger, resulted in suppressed oxidative stress and axonal injury. 47 The researchers suggest that the protective function of Edaravone may be mediated, in part, by down-regulation of neuronal nitric oxide synthase (NOS) and inducible NOS (iNOS) with a concomitant increase in iNOS and its free radical scavenging ability. Owing to the similarity in the potential mechanisms of MB as a free radical scavenger, MB could be limiting axonal injury by reducing the level of free radicals; however, additional studies are needed.…”

Section: Magnetic Resonance Imaging Characterization Of Traumatic Bramentioning

confidence: 99%

Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury

Watts

Long

Boggs

et al. 2016

Journal of Neurotrauma

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Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration-grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3 h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24 h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3 h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24 h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored.

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Attenuation of axonal injury and oxidative stress by edaravone protects against cognitive impairments after traumatic brain injury

Cited by 43 publications

References 42 publications

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Antioxidant therapies in traumatic brain injury: a review

Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury

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