Beneficial effect of dipyridyl, a liposoluble iron chelator against focal cerebral ischemia: In vivo and in vitro evidence of protection of cerebral endothelial cells

Méthy, D.; Bertrand, Nathalie; Prigent‐Tessier, Anne; Mossiat, Claude; Stanimirovic, Danica; Beley, A; Marie, Christine

doi:10.1016/j.brainres.2007.11.063

Cited by 22 publications

(15 citation statements)

References 34 publications

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“…Experimental use of H 2 O 2 as a model for acute oxidative stress has been employed to imitate the pathology of numerous neurological disorders including cerebral ischemia (Methy et al 2008;Wei et al 2011), Amyotrophic lateral sclerosis (Nani et al 2010), Parkinson's disease (Jenner 2003), Friedreich's ataxia (Anderson et al 2008), and Alzheimer's disease (Behl et al 1994;Miyata and Smith 1996). In addition to being a classic oxidative stress paradigm, H 2 O 2 has been shown to modulate neuromuscular activity in vertebrates (Giniatullin and Giniatullin 2003) and manipulate neuronal signal transduction in mammalian cell culture (Chai and Lin 2010).…”

Section: Discussionmentioning

confidence: 99%

A cGMP-dependent protein kinase (PKG) controls synaptic transmission tolerance to acute oxidative stress at the Drosophila larval neuromuscular junction

Caplan

Milton

2013

Journal of Neurophysiology

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Section: Discussionmentioning

confidence: 99%

A cGMP-dependent protein kinase (PKG) controls synaptic transmission tolerance to acute oxidative stress at the Drosophila larval neuromuscular junction

Caplan

Milton

2013

Journal of Neurophysiology

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“…Equally, it is far from clear how a simple conformational change of a protein leads to the vacuolation or spongiosis (e.g. Aguzzi 2006; Aguzzi et al 2007; Armstrong et al 2001; Chung et al 1999; Crozet et al 2008; Diedrich et al 1991; Foster et al 2001; Julius et al 2008; Kourie 2002; Mallucci et al 2003; Mallucci et al 2007; Miele et al 2001; Sakudo and Ikuta 2009a, b; Westaway et al 1994; Williams et al 1997) (formation of holes) in brain tissue characteristic of late-stage prion disease (and indeed of Alzheimer’s (Erkinjuntti et al 1996; Sakudo and Ikuta 2009a). The question then arises as to whether it is possible that PrP Sc modifies iron metabolism in an unfavourable way (and/or vice versa), not least since prion proteins bear phylogenetic relationships to the ZIP family of metal ion transporters (Schmitt-Ulms et al 2009).…”

Section: Prion Diseases: Including Transmissible Spongiform Encephalomentioning

confidence: 99%

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

2010

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Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions.

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“…Recent studies have shown that oxidative stress is a prominent feature of cerebral endothelial injury after cerebral ischemia (Maier et al, 2006;Jin et al, 2008). The lipophilic iron chelator dipyridyl was shown to prevent degeneration of CECs following photothrombotic ischemia (Methy et al, 2008). Thus, it is conceivable to reason that iron may mediate TJ protein loss and CEC degeneration after TFI.…”

Section: Levels Of [mentioning

confidence: 99%

Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats

et al. 2011

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Blood cells are transported into the brain and are thought to participate in neurodegenerative processes following hypoxic ischemic injury. We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction proteins, occludin, and zonula occludens-1, and degeneration of endothelial cells in the CA1-2 areas. Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical production and endothelial cell degeneration. Our findings suggest that iron overload and iron-mediated free radical production cause loss of tight junction proteins and degeneration of endothelial cells, opening of the BBB after TFI.

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Beneficial effect of dipyridyl, a liposoluble iron chelator against focal cerebral ischemia: In vivo and in vitro evidence of protection of cerebral endothelial cells

Cited by 22 publications

References 34 publications

A cGMP-dependent protein kinase (PKG) controls synaptic transmission tolerance to acute oxidative stress at the Drosophila larval neuromuscular junction

A cGMP-dependent protein kinase (PKG) controls synaptic transmission tolerance to acute oxidative stress at the Drosophila larval neuromuscular junction

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats

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