Effect of ibotenate on brain development: Excitotoxic mouse model of microgyria and posthypoxiclike lesions

Marret, Stéphane; Mukendi, R; Gadisseux, J-F.; Gressèns, Pierre; Evrard, P.

doi:10.1016/0887-8994(94)90216-x

Cited by 107 publications

(193 citation statements)

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“…Our model of i.c. ibotenate injection on P2 or P10 has been validated as accurately replicating excitotoxic lesions in human preterm or full-term neonates (21,27). Our findings regarding excitotoxic lesion severity when ibotenate is injected early after AUVL (PD2) are in line with the decreased incidence of short-term excitotoxic lesions in infants with IUGR.…”

Section: Discussionsupporting

confidence: 74%

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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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Section: Discussionsupporting

confidence: 74%

“…The brains were removed, fixed in 4% formaldehyde for 7 d, and embedded in paraffin. Former studies showed a strong correlation between the maximal radial and frontooccipital diameters of the ibotenate-induced lesions (18,21). Consequently, we cut serial 10-m sections from the frontal to the occipital pole in the coronal plane.…”

Section: Animalsmentioning

confidence: 99%

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

et al. 2011

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“…The fetal sheep cerebrum has a predilection for relatively selective WMI under conditions of moderate cerebral ischemia [41], whereas rodents have a propensity for mixed cerebral injury such that substantial gray matter injury accompanies WMI [47][48][49][50][51][52]. This shortcoming, for example, limits the relevance of rodent hypoxia-ischemia models for the study of myelination disturbances associated with chronic human WMI.…”

Section: Advantages and Disadvantages Of The Fetal Sheep To Model Wmimentioning

confidence: 99%

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

et al. 2012

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Despite advances in neonatal intensive care, survivors of premature birth remain highly susceptible to unique patterns of developmental brain injury that manifest as cerebral palsy and cognitive-learning disabilities. The developing brain is particularly susceptible to cerebral white matter injury related to hypoxia-ischemia. Cerebral white matter development in fetal sheep shares many anatomical and physiological similarities with humans. Thus, the fetal sheep has provided unique experimental access to the complex pathophysiological processes that contribute to injury to the human brain during successive periods in development. Recent refinements have resulted in models that replicate major features of acute and chronic human cerebral injury and have provided access to complex clinically relevant studies of cerebral blood flow and neuroimaging that are not feasible in smaller laboratory animals. Here, we focus on emerging insights and methodologies from studies in fetal sheep that have begun to define cellular and vascular factors that contribute to white matter injury. Recent advances include spatially defined measurements of cerebral blood flow in utero, the definition of cellular maturational factors that define the topography of injury and the application of high-field magnetic resonance imaging to define novel neuroimaging signatures for specific types of chronic white matter injury. Despite the higher costs and technical challenges of instrumented preterm fetal sheep models, they provide powerful access to clinically relevant studies that provide a more integrated analysis of the spectrum of insults that appear to contribute to cerebral injury in human preterm infants.

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“…Excessive activation of glutamate receptors may cause cell vulnerability, in part as a result of intracellular calcium influx (5,6). Intracerebral injection of glutamate agonists into the neocortex and white matter of newborn rodents produces histological lesions that mimic the brain damage observed in preterm neonates (7)(8)(9)(10).…”

mentioning

confidence: 99%

Vulnerability of white matter towards antenatal hypoxia is linked to a species-dependent regulation of glutamate receptor subunits

Fontaine

Olivier

Massonneau

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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White-matter damage is a leading cause of neurological handicap. Although hypoxia-ischemia and excitotoxicity are major pathogenic factors, a role for genetic influences was suggested recently. Thus, protracted gestational hypoxia was associated with whitematter damage (WMD) in rat pups but not in mouse pups. Indeed, microglial activation and vessel-wall density on postnatal days (P)1 and P10 were found increased in both mouse and rat pups, but cell death, astrogliosis, and myelination were only significantly altered in hypoxic rat pups. We investigated whether this species-related difference was ascribable to effects of antenatal hypoxia on the expression of glutamate receptor subunits by using immunocytochemistry, PCR, and excitotoxic double hit insult. Quantitative PCR in hypoxic mouse pups on P1 showed 2-to 4-fold down-regulation of the AMPA-receptor subunits -1, 2, and -4; of the kainate-receptor subunit GluR7; and of the metabotropic receptor subunits mGluR1, -2, -3, -5, and -7. None of the glutamate-receptor subunits was down-regulated in the hypoxic rat pups. NR2B was the only NMDA-receptor subunit that was down-regulated in hypoxic mice but not in hypoxic rat on P1. Ifenprodil administration to induce functional inhibition of NMDA containing NR2B-subunit receptors prevented hypoxia-induced myelination delay in rat pups. Intracerebral injection of a glutamate agonist produced a larger decrease in ibotenate-induced excitotoxic lesions in hypoxic mouse pups than in normoxic mouse pups. Gestational hypoxia may regulate the expression of specific glutamate-receptor subunits in fetal mice but not in fetal rats. Therefore, genetic factors may influence the susceptibility of rodents to WMD. brain damage ͉ NMDA receptors ͉ genetic factors ͉ development ͉ prematurity P eriventricular (P) WMD and subsequent cortical damage are the leading causes of cerebral palsy (CP) limited to preterm birth (1, 2). Animal models have been developed to unravel the mechanisms underlying these brain lesions. Factors that seem involved in the pathophysiology of CP in these models include hypoxia and ischemia, infection and inflammation, excitotoxicity, accumulation of reactive oxygen species, and deficiencies in growth factors (3, 4). These factors seem to act in combination to cause damage to the developing white matter.Glutamate accumulation may be a mechanism common to many risk factors for CP. Glutamate, the major excitatory neurotransmitter, acts by means of several groups of receptors, namely, NMDA, AMPA, kainate, and metabotropic receptors (mGluRs). Excessive activation of glutamate receptors may cause cell vulnerability, in part as a result of intracellular calcium influx (5, 6). Intracerebral injection of glutamate agonists into the neocortex and white matter of newborn rodents produces histological lesions that mimic the brain damage observed in preterm neonates (7-10).Several studies suggest that genetic factors may influence the susceptibility of very preterm infants to PWMD. The occurrence of CP may depend, at least in ...

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Effect of ibotenate on brain development: Excitotoxic mouse model of microgyria and posthypoxiclike lesions

Cited by 107 publications

References 0 publications

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

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

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

Vulnerability of white matter towards antenatal hypoxia is linked to a species-dependent regulation of glutamate receptor subunits

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