Neonatal hypoxic preconditioning involves vascular endothelial growth factor

Laudenbach, Vincent; Fontaine, R; Medja, Fadia; Carmeliet, Peter; Hicklin, Daniel J.; Gallego, Jorge; Leroux, Philippe; Marret, Stéphane; Gressèns, Pierre

doi:10.1016/j.nbd.2006.12.020

Cited by 50 publications

(34 citation statements)

References 62 publications

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“…Mice lacking eNOS expression show a greater degree of hemodynamic compromise after MCAO and hence the product of eNOS activity (i.e., NO) may protect the brain after focal cerebral ischemia by improving blood flow within the penumbral zone (Lo et al, 1996). VEGF can have a dual function in the brain mediating both neuroprotection and BBB permeability through VEGF/VEGFR2/Flk1 and PI3K/Akt pathways (Kilic et al, 2006;Laudenbach et al, 2007;Wang et al, 2007). Recently, DMOG treatment of rat pups after cerebral ischemia led to increased BBB permeability and brain edema in association with raised levels of VEGF (Chen et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection by Dimethyloxalylglycine following Permanent and Transient Focal Cerebral Ischemia in Rats

Nagel

Papadakis

Chen

et al. 2010

J Cereb Blood Flow Metab

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Dimethyloxalylglycine (DMOG) is an inhibitor of prolyl-4-hydroxylase domain (PHD) enzymes that regulate the stability of hypoxia-inducible factor (HIF). We investigated the effect of DMOG on the outcome after permanent and transient middle cerebral artery occlusion (p/tMCAO) in the rat. Before and after pMCAO, rats were treated with 40 mg/kg, 200 mg/kg DMOG, or vehicle, and with 40 mg/kg or vehicle after tMCAO. Serial magnetic resonance imaging (MRI) was performed to assess infarct evolution and regional cerebral blood flow (rCBF). Both doses significantly reduced infarct volumes, but only 40 mg/kg improved the behavior after 24 hours of pMCAO. Animals receiving 40 mg/kg were more likely to maintain rCBF values above 30% from the contralateral hemisphere within 24 hours of pMCAO. DMOG after tMCAO significantly reduced the infarct volumes and improved behavior at 24 hours and 8 days and also improved the rCBF after 24 hours. A consistent and significant upregulation of both mRNA and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was associated with the observed neuroprotection, although this was not consistently related to HIF-1a levels at 24 hours and 8 days. Thus, DMOG afforded neuroprotection both at 24 hours after pMCAO and at 24 hours and 8 days after tMCAO. This effect was associated with an increase of VEGF and eNOS and was mediated by improved rCBF after DMOG treatment.

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Section: Discussionmentioning

confidence: 99%

Neuroprotection by Dimethyloxalylglycine following Permanent and Transient Focal Cerebral Ischemia in Rats

Nagel

Papadakis

Chen

et al. 2010

J Cereb Blood Flow Metab

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“…This finding suggests that AUVL may alter NMDA receptor function downstream from receptor expression. The timing of the effect of AUVL on ibotenate toxicity, with a protective effect initially and a deleterious effect later on, suggests a transient preconditioning mechanism (16,17). Previous work suggests that VEGFs and their receptors may play pivotal roles in various preconditioning paradigms (9,16,25,26).…”

Section: Discussionmentioning

confidence: 99%

“…The timing of the effect of AUVL on ibotenate toxicity, with a protective effect initially and a deleterious effect later on, suggests a transient preconditioning mechanism (16,17). Previous work suggests that VEGFs and their receptors may play pivotal roles in various preconditioning paradigms (9,16,25,26). However, the mechanisms involved in the effects of AUVL seemed different from VEGFR2-mediated neuroprotection after postnatal hypoxia (16).…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, we showed that postnatal hypoxic preconditioning exerted protective effects in a murine model of excitotoxic brain lesions induced by intracerebral (i.c.) injections of the NMDA glutamate agonist ibotenate (16). This neuroprotective effect involves the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-2/Flk-1 pathway, which has neurotrophic and angiogenic properties (16).…”

mentioning

confidence: 99%

“…injections of the NMDA glutamate agonist ibotenate (16). This neuroprotective effect involves the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-2/Flk-1 pathway, which has neurotrophic and angiogenic properties (16). Few experimental studies focused on the potential for antenatal ischemic preconditioning to exert neuroprotective effects in the event of a neonatal insult.…”

mentioning

confidence: 99%

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Effects of Antenatal Uteroplacental Hypoperfusion on Neonatal Microvascularisation and Excitotoxin Sensitivity in Mice

et al. 2011

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Vascular intrauterine growth restriction (IUGR) occurs in about 5% of pregnancies and may reduce the incidence of periventricular leukomalacia in preterm newborns. We evaluated neonatal excitotoxicity in a murine model of vascular IUGR involving unilateral uterine ligation on embryonic day (E)13.5. Birth weight was significantly decreased in the ligation group compared with the sham group (p Ͻ 0.001). VEGFs, VEGF receptors (VEGFRs), and NMDA receptor subunit mRNAs in brain extracts were assayed using quantitative RT-PCR. Ligation was associated with increased mRNAs for the vascular marker PECAM-1 on postnatal day (PD)2 and VEGFR-3 on PD2 and PD10, contrasting with decreased VEGFA and VEGFC on PD10. Microvessel density was increased on PD7. Ligated and sham pups received intracerebral ibotenate (NMDA agonist) on PD2 or PD10.

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Association of Retinal Vascular Endothelial Growth Factor With Avascular Retina in a Rat Model of Retinopathy of Prematurity

2010

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Neonatal hypoxic preconditioning involves vascular endothelial growth factor

Cited by 50 publications

References 62 publications

Neuroprotection by Dimethyloxalylglycine following Permanent and Transient Focal Cerebral Ischemia in Rats

Neuroprotection by Dimethyloxalylglycine following Permanent and Transient Focal Cerebral Ischemia in Rats

Effects of Antenatal Uteroplacental Hypoperfusion on Neonatal Microvascularisation and Excitotoxin Sensitivity in Mice

Association of Retinal Vascular Endothelial Growth Factor With Avascular Retina in a Rat Model of Retinopathy of Prematurity

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