Temporal changes in free iron levels after brain ischemia

Millerot-Serrurot, Emilie; Bertrand, Nathalie; Mossiat, Claude; Fauré, Philippe; Prigent‐Tessier, Anne; Garnier, Philippe; Béjot, Yannick; Giroud, Maurice; Beley, A; Marie, Christine

doi:10.1016/j.neuint.2008.04.002

Cited by 33 publications

(17 citation statements)

References 48 publications

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“…It is this secondary spreading that is especially damaging, but because it is slower (4–7days), it also affords the opportunity for therapeutic intervention (Qureshi et al 2009). It is now clear that iron is intimately involved (Armengou and Davalos 2002; Bailey et al 2006; Bishop and Robinson 2001; Chang et al 2005; Dávalos, et al 1994; Demougeot et al 2004; Ferro and Dávalos 2006; Garoufi et al 2006; Gillum et al 1996; Lee et al 2006e; Marniemi et al 2005; Mascitelli and Pezzetta 2006; Mehta et al 2004; Mu et al 2005; Nakamura et al 2006; Saxena et al 2005; Selim and Ratan 2004; Switzer et al 2006; Wagner et al 2003; Wu et al 2003; Zuliani et al 2006; Adams 2007; Altamura et al 2009; Assenza et al 2009; Basak et al 2008; Bosomtwi et al 2008; Carbonell and Rama 2007; Cho et al 2007; Ekblom et al 2007; Hanson et al 2009; Heckl 2007; Helal 2008; Jolkkonen et al 2007; Justicia et al 2008; Kaushal and Schlichter 2008; Kim et al 2008a; Kobayashi et al 2008; Lou et al 2009; Maguire et al 2007; Mazumdar et al 2007; Mehdiratta et al 2008; Millan et al 2007, 2008; Millerot-Serrurot et al 2008; Nighoghossian et al 2008; O’Rourke et al 2008; Ratan et al 2008; Ross and Meschia 2009; Saleh et al 2007; Santhosh et al 2009; Verduzco and Nathan 2009; Walters and Rye 2009; Weng et al 2008), whether by release from (ferritin in) cells or from the haem of haemoglobin. Iron chelators have thus shown promise in decreasing the sequelae of an initial stroke-inducing event (Demougeot et al 2004; Ferro and Dávalos 2006; Hurn et al 1995; Kompala et al 1986; Mu et al 2005; Patt et al 1990; Prass et al 2002; Selim and Ratan 2004; Soloniuk et al …”

Section: Strokementioning

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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Section: Strokementioning

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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“…Iron has been frequently noted as a potential mediator for secondary injury following TBI due to its ability to form free radicals and induce oxidative stress 166167 Iron levels in the brain are elevated following TBI 168–171. While haem-bound iron from erythrocyte lysis is a significant contributor to this, it appears that this iron is supplemented by a release of endogenous sources of iron, suggesting that, like in forms of haemorrhage, the secondary cell loss associated with TBI allows subsequent iron release and a vicious cycle is thus perpetrated 167…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Brain iron overload following intracranial haemorrhage

et al. 2016

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Intracranial haemorrhages, including intracerebral haemorrhage (ICH), intraventricular haemorrhage (IVH) and subarachnoid haemorrhage (SAH), are leading causes of morbidity and mortality worldwide. In addition, haemorrhage contributes to tissue damage in traumatic brain injury (TBI). To date, efforts to treat the long-term consequences of cerebral haemorrhage have been unsatisfactory. Incident rates and mortality have not showed significant improvement in recent years. In terms of secondary damage following haemorrhage, it is becoming increasingly apparent that blood components are of integral importance, with haemoglobin-derived iron playing a major role. However, the damage caused by iron is complex and varied, and therefore, increased investigation into the mechanisms by which iron causes brain injury is required. As ICH, IVH, SAH and TBI are related, this review will discuss the role of iron in each, so that similarities in injury pathologies can be more easily identified. It summarises important components of normal brain iron homeostasis and analyses the existing evidence on iron-related brain injury mechanisms. It further discusses treatment options of particular promise.

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“…Lipid-soluble ferrous iron chelator 2,2′-dipyridyl (DP) has been reported to alleviate brain damage in different rodent models of cerebral ischemia (Demougeot et al, 2004; Methy et al, 2008; Millerot-Serrurot et al, 2008; Van Hoecke et al, 2005) and to reduce cerebral vasospasm in primate and rabbit models of subarachnoid hemorrhage (Horky et al, 1998; Yu et al, 2010). The lipid solubility of DP is evidenced by its ability to freely enter brain cells and chelate intracellular free iron, thereby reducing iron-induced cell death (Breuer et al, 1995; Kress et al, 2002; Methy et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of the lipid-soluble iron chelator 2,2′-dipyridyl against hemorrhagic brain injury

et al. 2012

Neurobiology of Disease

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Previous studies have indicated that 2,2′-dipyridyl, a lipid-soluble ferrous iron chelator, can reduce brain injury after cerebral ischemia and reduce cerebral vasospasm after subarachnoid hemorrhage. In this study, we examined the efficacy of 2,2′-dipyridyl after intracerebral hemorrhage (ICH) in 12-month-old mice. ICH was modeled by intrastriatal injection of collagenase or autologous whole blood. 2,2′-Dipyridyl or vehicle was administered intraperitoneally 2 h before ICH (pretreatment) or 6 h after ICH (post-treatment) and then once daily for up to 3 days. Mice in the pretreatment group were sacrificed 1 or 3 days after ICH and examined for iron deposition, neuronal death, oxidative stress, microglial/astrocyte activation, neutrophil infiltration, and white matter damage. Mice in the post-treatment group were examined for brain lesion volume and edema on day 3 and for neurologic deficits on days 1, 3, and 28 after ICH. Pretreatment with 2,2′-dipyridyl decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, reduced microglial activation without affecting astrocytes or neutrophil infiltration, and attenuated white matter damage. Post-treatment reduced brain lesion volume and edema and improved neurologic function. These results indicate that the lipid-soluble ferrous iron chelator 2,2′-dipyridyl can reduce brain injury and improve functional outcome after ICH.

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Temporal changes in free iron levels after brain ischemia

Cited by 33 publications

References 48 publications

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

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

Brain iron overload following intracranial haemorrhage

Efficacy of the lipid-soluble iron chelator 2,2′-dipyridyl against hemorrhagic brain injury

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