Effect of a Free Radical Scavenger, Edaravone, in the Treatment of Patients With Aneurysmal Subarachnoid Hemorrhage

Munakata, Akira; Ohkuma, Hiroki; Nakano, Takahiro; Shimamura, Norihito; Asano, Kenichirou; Naraoka, Masato

doi:10.1227/01.neu.0000338067.83059.eb

Cited by 69 publications

(49 citation statements)

References 45 publications

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“…It has been shown that SAH causes an imbalance between vasoconstrictors and vasodilators, which is mainly responsible for the neurological deficits, is closely related to the generation of ROS [56]. Several experimental and human studies have shown that inhibition of ROS by several antioxidant compounds decreased SAH-induced cerebral vasospasm and ischemia [14,15] In the present study, luminol Cl levels, which detect • OH, H 2 O 2 , HOCl radicals, as well as lucigenin CL levels detecting O 2 -were significantly increased, implicating that SAH causes increased ROS production in the cerebral tissue and ALA treatment significantly inhibited SAH-induced ROS production. The CL results of the current study are in agreement with a number of studies which show that ALA and its reduced form DHLA directly scavenge reactive oxygen and nitrogen species [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the use of free radical scavengers in animal models of SAH [11,12] and some clinical trials [13,14] have demonstrated beneficial effects of these agents on ischemic neurological deficits due to SAH-induced vasospasms. We have recently shown that melatonin, which is a potent free radical scavenger, reversed SAH-induced histopathological and biochemical alterations [15].…”

Section: Introductionmentioning

confidence: 99%

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Alpha Lipoic Acid Alleviates Oxidative Stress and Preserves Blood Brain Permeability in Rats with Subarachnoid Hemorrhage

et al. 2009

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The neuroprotective effect of alpha lipoic acid (ALA; 100 mg/kg, po), a dithiol antioxidant, on experimentally induced subarachnoid hemorrhage (SAH) was assessed in Wistar albino rats. Neurological examination scores recorded at the 48th h of SAH induction were increased in SAH groups, which were accompanied with significant increases in the formation of reactive oxygen species, DNA fragmentation ratios, malondialdehyde levels and myeloperoxidase activity, while significant decreases in the brain glutathione content and Na(+), K(+)-ATPase activity were observed. On the other hand, ALA treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations. Increased brain edema, impaired blood-brain-barrier permeability and neurological scores were also improved by ALA treatment. The results demonstrate that ALA exerts neuroprotective effects via the enhancement of endogenous antioxidant enzyme activity, the inhibition of neutrophil accumulation and free radical generation, suggesting a therapeutic potential in reducing secondary injury after SAH in patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alpha Lipoic Acid Alleviates Oxidative Stress and Preserves Blood Brain Permeability in Rats with Subarachnoid Hemorrhage

et al. 2009

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“…The detailed pathogenesis of cerebral vasospasm remains unclear and, in spite of intense and extensive investigations over the past four decades, no optimal treatment has been established (21). Recently, Munakata et al reported a trend toward a lesser incidence of delayed ischemic neurological deficits and a lesser incidence of poor outcome caused by cerebral vasospasm in edaravone-treated patients (22). Edaravone was found to exhibit a clear and selective inhibitory effect against hydroxyl radical-induced vasocontraction in the canine basilar artery in vitro (23).…”

Section: Effects Of Edaravone On Various Neurologic Diseases That Do mentioning

confidence: 99%

Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction

Kikuchi¹,

Kikuchi

Uchikado

et al. 2011

Experimental and Therapeutic Medicine

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“…Edaravone is a strong scavenger of hydroxyl radicals [11,12,13,14,15,16,17]. It has an inhibitory effect on lipid peroxidation by scavenging free radicals, and it prevents vascular endothelial cell injury [14].…”

Section: Introductionmentioning

confidence: 99%

“…It has an inhibitory effect on lipid peroxidation by scavenging free radicals, and it prevents vascular endothelial cell injury [14]. In 2001, edaravone was approved in Japan for the treatment of acute brain infarction within 24 h of onset, and it has been in clinical use for this treatment since then [11,13,14]. Although there are plenty of clinical and experimental studies on edaravone that report its effectiveness on acute cerebral ischemic incidences, trials on its effect after SCI are relatively restricted [11,12,15,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Edaravone on Experimental Spinal Cord Injury in Rats

Özgiray¹,

Serarslan²,

Öztürk

et al. 2011

Pediatr Neurosurg

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Background: Spinal cord injury (SCI) is a leading cause of morbidity and mortality among youth and adults. Secondary injury mechanisms within the spinal cord (SC) are well known to cause deterioration after an acute impact. Free radical scavengers are among the most studied agents in animal models of SCI. Edaravone is a scavenger of hydroxyl radicals. Methods: We aimed to measure and compare the effects of both methylprednisolone and edaravone on tissue and on serum concentrations of nitric oxide (NO), malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and tissue total antioxidant capacity (TAC) in rats with SCI. SCI was induced in four groups of Wistar albino rats by a weight-drop method. The neurological function of the rats was periodically tested. At the end of the experiment, blood samples were collected, and SC tissue samples were harvested for biochemical evaluation. Results: The tissue level of NO was decreased in the edaravone-treated group compared with the no-treatment group (p < 0.05). The tissue levels of SOD and GSH-Px were higher in the edaravone-treated group than in the no-treatment group (p < 0.05). The serum levels of NO were lower in the edaravone-treated and methylprednisolone-treated groups than in the no-treatment group (p < 0.05). The serum levels of SOD in the edaravone-treated group did not differ from those of any other group. The serum levels of MDA in the edaravone-treated and no-treatment groups were higher than in the two other groups (p < 0.05). Tissue levels of MDA in the edaravone-treated group were lower than in the no-treatment group (p < 0.05). Tissue levels of TAC in the edaravone-treated group were higher than in the no-treatment and methylprednisolone-treated groups (p < 0.05). The neurological outcome scores of the animals in treatment groups did not depict any statistically significant improvement in motor functions. However, edaravone seemed to prevent further worsening of the immediate post-SCI neurological status. Conclusion: Our biochemical analyses indicate that edaravone is capable of blunting the increased oxidative stress that follows SCI. We show, for the first time, that edaravone enhances the TAC in SC tissue. This beneficial effect of edaravone on antioxidant status may act to minimize the secondary neurological damage that occurs during the acute phase after SCI.

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Effect of a Free Radical Scavenger, Edaravone, in the Treatment of Patients With Aneurysmal Subarachnoid Hemorrhage

Abstract: We found a trend toward a lesser incidence of DINDs and a lesser incidence of poor outcome caused by cerebral vasospasm in edaravone-treated patients. It might therefore be suggested that edaravone is a useful agent for the treatment of aneurysmal SAH.

Cited by 69 publications

References 45 publications

Alpha Lipoic Acid Alleviates Oxidative Stress and Preserves Blood Brain Permeability in Rats with Subarachnoid Hemorrhage

Alpha Lipoic Acid Alleviates Oxidative Stress and Preserves Blood Brain Permeability in Rats with Subarachnoid Hemorrhage

Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction

Protective Effects of Edaravone on Experimental Spinal Cord Injury in Rats

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