Inhibition of Iron-Dependent and Ischemia-Induced Brain Damage by the α-Tocopherol Analogue MDL 74,722

Worp, H.Bernardus van der; Thomas, Craig E.; Kappelle, L. Jaap; Hoffman, Wherly; Wildt, Dick J. De; Bär, P.R.

doi:10.1006/exnr.1998.6968

Cited by 14 publications

(5 citation statements)

References 19 publications

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“…Various antioxidants such as vitamins, lipoic acid (LA), and N -acetylcysteine have been tested for efficacy in stroke [118]. Vitamin E and its analog MDL 74,722 have been reported to reduce lesion volume and behavioral impairments in rodent ischemic stroke models [119–121]. Alternatively, a follow-up study in human subjects demonstrated that vitamin E and C did not reduce the risk of ischemic stroke and did not enhance functional recovery in stroke patients, respectively [122–124].…”

Section: Key Pathological Events and Pathways Fueling Neuroinflammationmentioning

confidence: 99%

Neuroinflammation: friend and foe for ischemic stroke

Jayaraj

Azimullah

Beiram

et al. 2019

J Neuroinflammation

957

695

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Stroke, the third leading cause of death and disability worldwide, is undergoing a change in perspective with the emergence of new ideas on neurodegeneration. The concept that stroke is a disorder solely of blood vessels has been expanded to include the effects of a detrimental interaction between glia, neurons, vascular cells, and matrix components, which is collectively referred to as the neurovascular unit. Following the acute stroke, the majority of which are ischemic, there is secondary neuroinflammation that both promotes further injury, resulting in cell death, but conversely plays a beneficial role, by promoting recovery. The proinflammatory signals from immune mediators rapidly activate resident cells and influence infiltration of a wide range of inflammatory cells (neutrophils, monocytes/macrophages, different subtypes of T cells, and other inflammatory cells) into the ischemic region exacerbating brain damage. In this review, we discuss how neuroinflammation has both beneficial as well as detrimental roles and recent therapeutic strategies to combat pathological responses. Here, we also focus on time-dependent entry of immune cells to the ischemic area and the impact of other pathological mediators, including oxidative stress, excitotoxicity, matrix metalloproteinases (MMPs), high-mobility group box 1 (HMGB1), arachidonic acid metabolites, mitogen-activated protein kinase (MAPK), and post-translational modifications that could potentially perpetuate ischemic brain damage after the acute injury. Understanding the time-dependent role of inflammatory factors could help in developing new diagnostic, prognostic, and therapeutic neuroprotective strategies for post-stroke inflammation.

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Section: Key Pathological Events and Pathways Fueling Neuroinflammationmentioning

confidence: 99%

Neuroinflammation: friend and foe for ischemic stroke

Jayaraj

Azimullah

Beiram

et al. 2019

J Neuroinflammation

957

695

View full text Add to dashboard Cite

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“…[ 109 110 111 ] MDL 74,722, a Vitamin E analog, has been reported to reduce lesion volume in the rat MCAO model. [ 112 ] It has been reported that Vitamin C is protective in both rodent and primate models of ischemic stroke. [ 113 114 115 ] However, a follow-up study in human showed that food supplement of Vitamin E and Vitamin C did not reduce the risk for ischemic stroke.…”

Section: Therapeutic Strategies To Reduce Oxidative Stress For Treatmmentioning

confidence: 99%

Targeting oxidative stress for the treatment of ischemic stroke: Upstream and downstream therapeutic strategies

Yang

2016

Brain Circ

102

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Excessive oxygen and its chemical derivatives, namely reactive oxygen species (ROS), produce oxidative stress that has been known to lead to cell injury in ischemic stroke. ROS can damage macromolecules such as proteins and lipids and leads to cell autophagy, apoptosis, and necrosis to the cells. This review describes studies on the generation of ROS, its role in the pathogenesis of ischemic stroke, and recent development in therapeutic strategies in reducing oxidative stress after ischemic stroke.

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“…67 When the alpha tocopherol analogue, 2,3-dihydro-2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)-methyl]-1-denzofuran-5-ol dihydrochloride (MDL 74,180) was added to cerebellar granule cell cultures before treatment with iron, brain injury, and cell toxicity were attenuated. 68 Similarly, even transient alpha tocopherol administration to hippocampal neurons results in decreased iron-induced oxidative damage. 69 Histology, topography, and in vivo characterization of brain iron with aging Microscopic iron distribution.…”

Section: Endogenous Protection From Iron-related Damagementioning

confidence: 99%

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

et al. 2007

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Summary:Iron is important for brain oxygen transport, electron transfer, neurotransmitter synthesis, and myelin production. Though iron deposition has been observed in the brain with normal aging, increased iron has also been shown in many chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In vitro studies have demonstrated that excessive iron can lead to free radical production, which can promote neurotoxicity. However, the link between observed iron deposition and pathological processes underlying various diseases of the brain is not well understood. It is not known whether excessive in vivo iron directly contributes to tissue damage or is solely an epiphenomenon. In this article, we focus on the imaging of brain iron and the underlying physiology and metabolism relating to iron deposition. We conclude with a discussion of the potential implications of iron-related toxicity to neurotherapeutic development.

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Inhibition of Iron-Dependent and Ischemia-Induced Brain Damage by the α-Tocopherol Analogue MDL 74,722

Cited by 14 publications

References 19 publications

Neuroinflammation: friend and foe for ischemic stroke

Neuroinflammation: friend and foe for ischemic stroke

Targeting oxidative stress for the treatment of ischemic stroke: Upstream and downstream therapeutic strategies

Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications

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