Cytoprotective Efficacy and Mechanisms of the Liposoluble Iron Chelator 2,2′-Dipyridyl in the Rat Photothrombotic Ischemic Stroke Model

Demougeot, Céline; Hoecke, Michaël Van; Bertrand, Nathalie; Prigent‐Tessier, Anne; Mossiat, Claude; Beley, A; Marie, Christine

doi:10.1124/jpet.104.072744

Cited by 71 publications

(58 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although HIF-1α largely participates in the adaptive response during hypoxia (Sharp and Bernaudin, 2004), paradoxically it also might mediate hypoxic cell death (Carmeliet et al, 1998;Bruick, 2003;Vangeison et al, 2008). In CNS, induction and expression of HIF-1α after an ischemic insult is heterogeneous (Demougeot et al, 2004) and it has been described to play both neuroprotective and detrimental effects depending on the severity of the insult (Helton et al, 2005;Baranova et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…During an ischemic insult, HIF-1α levels decrease gradually from the ischemic core to more distant regions (Demougeot et al, 2004) indicating that induction and expression of HIF-1α in ischemic areas is heterogeneous. Moreover, both neuroprotective and detrimental effects of HIF-1α have been observed in different models of ischemia (Halterman et al, 1999;Siddiq et al, 2005;Helton et al, 2005;Baranova et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HIF-1α is neuroprotective during the early phases of mild hypoxia in rat cortical neurons

López-Hernández

Posadas

Podlesniy

et al. 2012

Experimental Neurology

View full text Add to dashboard Cite

Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays a key role regulating the adaptive response to hypoxia. HIF-1α is stabilised during hypoxia and, after dimerization with HIF-1β, triggers the expression of different genes involved in cell cycle control and energy metabolism associated with cell survival. However, HIF-1α also regulates the expression of proapoptotic genes. The aim of this work is to ascertain the influence of HIF-1α on neurotoxicity evoked by hypoxia in rat cortical neurons. We found that mild hypoxia induces a time-dependent neuronal death that involves free radical production, mitochondrial depolarization, cytochrome c release and caspase 3 activation. Lentiviral mediated knockdown of HIF-1α markedly potentiated all these effects during the initial 24 hours of hypoxia suggesting that HIF-1α plays a neuroprotective role on hypoxia-mediated neuronal death. After this period, the protective actions of HIF-1α disappeared in agreement with the time-course of hypoxia-mediated HIF-1α stabilization. On the other hand, lentiviral mediated over expression of HIF-1α increased lactate dehydrogenase A, one of the target genes for HIF-1α, but did not show protective actions on hypoxia-mediated neuronal death indicating that the level of endogenous HIF-1α stabilization achieved during hypoxia is already the maximal required for the transcription activities of HIF-1α. These results indicate that HIF-1α is neuroprotective in the early phases of hypoxia.3

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HIF-1α is neuroprotective during the early phases of mild hypoxia in rat cortical neurons

López-Hernández

Posadas

Podlesniy

et al. 2012

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…Inhibitors of prolyl hydroxylases have been tested recently for their ability to induce HIF-1␣ stabilization and subsequent expression of target genes in cultured cells as well as in vivo Demougeot et al, 2004). Among them, previous reports indicated that 3,4-dihydroxybenzoic acid, deferoxamine (DFO), and DP have neuroprotective effects against brain ischemia (Demougeot et al, 2004;Van Hoecke et al, 2005;Siddiq et al, 2005;Freret et al, 2006).…”

Section: Lesser Severity Of Brain Ischemia Damage By Treatment With Pmentioning

confidence: 99%

“…Among them, previous reports indicated that 3,4-dihydroxybenzoic acid, deferoxamine (DFO), and DP have neuroprotective effects against brain ischemia (Demougeot et al, 2004;Van Hoecke et al, 2005;Siddiq et al, 2005;Freret et al, 2006). However, it is unclear whether these agents act solely on the HIF pathway.…”

Section: Lesser Severity Of Brain Ischemia Damage By Treatment With Pmentioning

confidence: 99%

Neuron-Specific Inactivation of the Hypoxia Inducible Factor 1 Increases Brain Injury in a Mouse Model of Transient Focal Cerebral Ischemia

Baranova¹,

Miranda²,

Pichiule³

et al. 2007

Journal of Neuroscience

324

328

View full text Add to dashboard Cite

In the present study, we show a biphasic activation of hypoxia inducible factor 1␣ (HIF-1) after stroke that lasts for up to 10 d, suggesting the involvement of the HIF pathway in several aspects of the pathophysiology of cerebral ischemia. We provide evidence that HIF-1-mediated responses have an overall beneficial role in the ischemic brain as indicated by increased tissue damage and reduced survival rate of mice with neuron-specific knockdown of HIF-1␣ that were subjected to transient focal cerebral ischemia. In addition, we demonstrated that drugs known to activate HIF-1 in cultured cells as well as in vivo had neuroprotective properties in this model of cerebral ischemia. This protective effect was significantly attenuated but not completely abolished in neuron-specific HIF-1␣-deficient mice, suggesting that alternative mechanisms of neuroprotection are also implicated. Last, our study showed that hypoxia-induced tolerance to ischemia was preserved in neuron-specific HIF-1␣-deficient mice, indicating that the neuroprotective effects of hypoxic preconditioning do not depend on neuronal HIF-1 activation.

show abstract

“…The degree of blood-brain barrier (BBB) disruption was assessed by the measurement of Evans blue dye leakage (Uyama et al, 1988;Demougeot et al, 2004) with slight modifications. Briefly, 1% Evans blue (Sigma) in saline was injected (3 ml/kg, i.v.)…”

Section: Assessment Of Blood-brain Barrier Permeabilitymentioning

confidence: 99%

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Shin

Kang

Lee

et al. 2009

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

ABBREVIATIONS: SSRIs, serotonin reuptake inhibitors; HO-1, heme oxygenase-1; HIF-1α, hypoxia-inducible factor-1α; BBB, blood-brain barrier; rCBF, regional cerebral blood flow; MABP, mean arterial blood pressure; LL, lower limit; HSP-32, heat-shock protein. Medicine, Korea This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine-and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1α (HIF-1α) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1α proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

show abstract

Cytoprotective Efficacy and Mechanisms of the Liposoluble Iron Chelator 2,2′-Dipyridyl in the Rat Photothrombotic Ischemic Stroke Model

Cited by 71 publications

References 47 publications

HIF-1α is neuroprotective during the early phases of mild hypoxia in rat cortical neurons

HIF-1α is neuroprotective during the early phases of mild hypoxia in rat cortical neurons

Neuron-Specific Inactivation of the Hypoxia Inducible Factor 1 Increases Brain Injury in a Mouse Model of Transient Focal Cerebral Ischemia

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Contact Info

Product

Resources

About