The role of free radicals in cerebral hypoxia and ischemia

Abstract:Reactive oxygen species (ROS) are widely believed to cause or aggravate several human pathologies such as neurodegenerative diseases, cancer, stroke and many other ailments. Antioxidants are assumed to counteract the harmful effects of ROS and therefore prevent or treat oxidative stress-related diseases. In this report, recent human studies exploring the efficiency of antioxidants in prevention and treatment of various diseases are reviewed. Few antioxidants including edaravone (for ischemic stroke in Japan), Nacetylcysteine (for acetaminophen toxicity), alfa-lipoic acid (for diabetic neuropathy) and some flavonoids (polyphenolic compounds present in dietary plants), such as micronized purified flavonoid fraction (diosmin and hesperidin) and oxerutins (for chronic venous insufficiency) as well as baicalein and catechins (for osteoarthritis) have found accepted clinical use. However, despite much enthusiasm in the 1980s and 1990s, many well-known agents such as antioxidant vitamins and also more recently developed compounds such as nitrones have not successfully passed the scrutiny of clinical trials for prevention and treatment of various diseases. This has given rise to a pessimistic view of antioxidant therapy, however, the evidence from human epidemiological studies about the beneficial effects of dietary antioxidants and preclinical in vitro and animal data are compelling. We have probably wasted too much time on agents like antioxidant vitamins instead of focusing on more disease specific, target-directed, highly bioavailable antioxidants. We here discuss possible reasons for the lack of success in some clinical trials and seek to provide some suggestions to be considered if antioxidant therapy is to succeed as an effective therapeutic strategy.

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“…The important role of ROS in ischemic stroke has been studied by many investigators [20,21] and reviewed in [227] and [228].…”

Section: Strokementioning

confidence: 99%

Clinical and pharmacological aspects of bath salt use: A review of the literature and case reports

Miotto¹,

Striebel²,

Cho

et al. 2013

Drug and Alcohol Dependence

121

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“…Although hyperemia causes excessive release of activated catabolic enzymes and free radicals (Colbourne et al, 1999;Wang et al, 2011;Werner and Engelhard, 2007) resulting in neuronal cell injury shortly after ischemia, hypoperfusion induced mitochondrial depletion and excessive release of excitatory neurotransmitter, reactive oxygen species, and peroxynitrite (Brown and Borutaite, 2006;Murphy and Gibson, 2007;Rodrigo et al, 2005;Takizawa et al, 2002) all can play a crucial role in the pathogenesis of neuronal cell death following ischemia (Sarti et al, 2002). Neurons in the CA1 region of the hippocampus can play a critical role in the spatial learning/memory formation, which is most vulnerable to ischemia (Abe et al, 1995).…”

Section: Cellular Metabolismmentioning

confidence: 99%

Fatty acid methyl esters as a potential therapy against cerebral ischemia

Lee

Vasquez

Klein

et al. 2015

OCL

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-Saturated fatty acids have been traditionally thought to be detrimental in circulation. However, we describe the beneficial effects of palmitic and stearic acid methyl esters as it relates to neuroprotection and cerebral vasodilatory properties in global and focal cerebral ischemia. The methyl esterification of fatty acids is not prominent in nature. However, it seems to have biological activity related to neuroprotection/vasodilation. We will discuss the etiology of cerebral ischemia such as stroke and cardiac arrest in terms of current and future treatment modalitiesas it relates to fatty acid-based therapies. This review is based on the meeting presentation at the "The Journées Chevreul, Lipids & Brain III 2015" in Paris on 16-18 March, 2015.Keywords: Cerebral ischemia / cerebral blood flow / neuroprotection / palmitic acid methyl ester / protein arginine methyltransferase Résumé -Les esters méthyliques d'acides gras comme possible thérapie contre l'ischémie cérébrale. Les acides gras saturés ont été de longue date considérés comme délétères pour la circulation sanguine. Cependant, nous décrivons dans cet article les effets bénéfiques d'esters méthyliques d'acides palmitique et stéarique en ce qui concerne la neuroprotection, ainsi que les propriétés de vasodilatation au niveau cérébral face à l'ischémie cérébrale globale et focale. L'estérification méthylique d'acides gras n'est pas très répandue dans la nature. Cependant, elle semble avoir une activité biologique neuroprotectrice/vasodilatatrice. Nous discutons, dans cet article, de l'étiologie de l'ischémie cérébrale de type AVC et arrêt cardiaque, et ce en termes de modalités de traitement, actuels et futurs, en ce qui concerne les thérapies à base d'acide gras. Cette revue est basée sur la présentation faite à l'occasion de la conférence « Les Journées Chevreul, Lipids & Brain III 2015 » qui s'est tenue à Paris les 16-18 Mars 2015.Mots clés : Ischémie cérébrale / circulation sanguine cérébrale / neuroprotection / ester méthylique d'acide palmitique / arginine méthyltransférase

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“…As previously described, physiopathological mechanisms leading to neuronal injury in cerebral stroke are complex and multifactorial. However, several studies suggest that oxidative stress, secondary to ROS and RNS production, actively participates during postischemic brain damage (Peters et al, 1998;Rodrigo et al, 2005). During ischemia, free radical production in the infarct zone decreases or remains without change, while it increases during reperfusion.…”

Section: Ischemiamentioning

confidence: 99%