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Biomedical subjects

S Marret

Publications and source records attributed to S Marret.

At least 19 recordsLinked to original sources
PubMed1999

Glycine antagonist and NO synthase inhibitor protect the developing mouse brain against neonatal excitotoxic lesions.

The prevention of cerebral palsy and neuroprotection of the immature brain continue to be health care priorities. The pathophysiology of perinatal brain lesions associated with cerebral palsy seems to be multifactorial and includes pre- and perinatal factors such as preconceptional events, hormone and growth factors deficiencies, maternal infections with production of cytokines, and hypoxic/ischemic perfusion failures. Excitotoxic cascade could represent a common pathway that leads to neural cell death and subsequent brain damage. Brain injuries induced by ibotenate, a glutamatergic analog, which are essentially mediated through the N-methyl-D-aspartate receptor, mimic some aspects of the white matter cysts and transcortical necrosis observed in human perinatal brain damage. The purpose of the present study was to assess the protective role of several pharmacological agents, administered in conjunction with ibotenate, against induced excitotoxic lesions. We injected ibotenate in the developing mouse brain 5 d postnatally, after the full settlement of neuronal layers. Co-treatment with kynurenic acid, an antagonist of the facilitating glycine site of the N-methyl-D-aspartate receptor, or with N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, induced a dose-dependent neuroprotective effect. Conversely, zinc gluconate, a blocking agent of the channel linked to the N-methyl-D-aspartate receptor, and a free radical scavenger (U74389F), were unable to protect the developing brain against excitotoxic attack. These data help to clarify some molecular mechanisms involved in excitotoxic lesions of the developing mouse brain and permit us to envision new strategies in the prevention of cerebral palsy.

Animals↗
PubMed1999

Fetal lactic dehydrogenase variation in normal pregnancy and in cases of severe intra-uterine growth restriction.

Physiological and pathological fetal levels of lactic dehydrogenase (LDH), including its five different iso-enzymes are still poorly known. Our objectives were to compare total LDH levels and its five iso-enzymes between a control group of healthy fetuses and a group of fetuses with severe intra-uterine growth restriction (IUGR), and to determine the biochemical associations and the prognostic value of elevated LDH activity in fetuses with IUGR. Total LDH levels, haematologic values and liver enzyme activities were measured in 108 healthy fetuses from 17 to 37 weeks of gestation and in 44 fetuses with severe IUGR. Total fetal LDH in plasma from the healthy fetuses were constant throughout pregnancy (mean (SD)= 305.09 (46.97)). Total LDH values in plasma significantly increased in cases of IUGR (p=0.003), and the degree of increase was significantly correlated with fetal erythroblastosis (n =44, r=0.80, p<0.001). LDH 5 significantly decreased in the IUGR group (p=0.03). Total LDH values strictly above 400 IU/l (a value equal to the mean+2 SD in the healthy fetus group) were found to be significantly associated with thrombocytopenia (p<0.001), erythroblastosis (p=0.008) and an increase in AST value (p=0.03). These results suggest that the fetal LDH value in plasma is a useful biological marker for severe chronic distress.

Case-Control Studies↗
PubMed1998

Long-term evolution of excitotoxic cortical dysgenesis induced in the developing rat brain.

Cortical dysplasias are frequently caused by excitotoxic brain damage due to hypoxia or ischemia during development. Ibotenate, a glutamatergic agonist, was injected in the neopallium of rat pups at day of birth. The resulting cytoarchitectonic pattern includes neuronal depopulation in deep cortical layers, sulcus formation, and molecular ectopias, mimicking human polymicrogyria and disorders of neuronal migration. These cortical dysplasias persist until adulthood, providing a rat model to investigate the long-term functional consequences of cortical malformations.

Abnormalities, Drug-Induced↗
PubMed1998

[Localized neonatal convulsions and cerebral arterial infarction].

BACKGROUND: Stroke is a rare cause of neonatal seizures. CASE REPORTS: During a 5-year period, eight full-term infants were admitted to hospital for seizures due to a stroke. Seizures began shortly after birth and were always one-sided. Early CT scans showed cerebral infarctions. Motor disabilities such as hemiparesis were found in three out of seven cases; language difficulties were observed in the same proportion; however all the children had not reached school age. CONCLUSION: Neonatal localized seizures may be symptomatic of a stroke and therefore justify a computerized tomography (CT) scan. Motor and cognitive sequelae require early management.

Cerebral Infarction↗
PubMed1998

[Focal dermal hypoplasia: description of three cases].

BACKGROUND: Focal dermal hypoplasia syndrome is mainly defined by the association of abnormalities of extremities, atrophy and linear hyperpigmentation of the skin, localized deposits of superficial fat, anomalies of the eyes and of the nails. Neonates are often small for their age. CASE REPORTS: Three sporadic cases are reported. Mental delay and omphalocele were observed in the first case. The neurological development was subnormal in the second and an unusual monodactyly was seen in the third. CONCLUSION: Most cases are sporadic, but in family cases, an X-linked dominant factor is likely. When a first affected offspring is observed, skin examination and X-ray should be carried out in parents to evaluate the risk of recurrence in their children. As the gene site has not yet been determined, antenatal diagnosis should be suspected on echography when fetal growth delay is associated to distal limb and/or ocular anomalies.

Child↗
PubMed1998

[Periventricular leukomalacia. I. Histological and pathophysiological aspects].

The term 'periventricular leukomalacia' (PVL) usually covers necrotic and/or gliotic lesions from perinatal origin occurring in the periventricular ring of telencephalic white matter. PVLs are found post-mortem in one third of brains from autopsies of premature infants; PVLs are diagnosed in 4 to 10% of infants born before 33 weeks of gestation and remaining alive more than 3 days after birth. PVL is very rare in at term infants. The proportion of PVLs from prenatal origin is estimated between one third and one half of cases. Recent progresses in neuroepidemiology, developmental neurobiology and imaging methods permit to revisit the pathophysiology of PVLs on a multifactorial basis. The final result of these multiple factors seem to be calcium influx due to glutamatergic overactivation triggered by cytokines, infection and inflammation, and deficit in neurotrophic factors. Periventricular topography can be explained by properties of intracerebral vascular wall at this stage of angiogenesis and by perfusion failure/hypoxia.

Humans↗
PubMed1998

[Periventricular leukomalacia and brain protection. II. Diagnosis, sequelae and neuroprotection].

The term 'periventricular leukomalacia' (PVL) usually covers necrotic and/or gliotic lesions from perinatal origin occurring in the periventricular ring of telencephalic white matter. Carrying motor and neuropsychological consequences, PVLs could be the most severe danger for very premature brains. Positive rolandic sharp waves recorded on EEG and precocious abnormally echogenous periventricular images on ultrasound suggest prospective periventricular cysts. Cystic periventricular cavitations certify the diagnosis of PVL. More subtle lesions of PVL do not reach the cystic grade and their diagnosis is confirmed by MRI. Treatment of infections is already available and potentially a tool for prevention. When the overwhelming glutamatergic signal has been triggered, neuroprotective agents turning off the excitotoxic cascade, including calcium blockers, growth factors and others, are promising therapeutic tools.

Humans↗
PubMed1998

[Emergency electroencephalography during perinatal cerebral intensive care: indications and results].

The main contribution of EEG during intensive care in infants with hypoxic-ischemic encephalopathy is i) to help determine whether infants with subtle clinical manifestations present with epileptic seizures, ii) to determine whether paralyzed or heavily sedated infants present with convulsive phenomena, iii) to assess the therapeutical response to anticonvulsants, 4) to contribute, in combination with ultrasound scanning, to diagnostic evaluation of the severity of lesions, and to provide valuable prognostic informations via the analysis of the background activity, as normal EEG is highly predictive of normal outcome, whereas various abnormal EEG features are constantly associated with subsequent major neurological abnormalities or death. These EEG features are readily available from a very early stage and may both precede and be prognostically more sensitive than information obtained from ultrasound. Recording of neonatal electroencephalogram requires awareness of the normal development of electroencephalographic features in the newborn, skilled technicians, and experienced readers of EEG tracings.

Brain Ischemia↗
PubMed1998

Hyaluronectin is produced by oligodendrocytes and Schwann cells in vitro.

A hyaluronectin (HN)-like antigen was found in rat O-2A progenitors and oligodendrocytes, as well as in Schwann cells and in their culture medium. The HN-like antigen secreted in culture supernatants had a higher molecular mass than HN extracted from rat brain at acidic pH. In vitro the secreted HN-like antigen was spontaneously and slowly degraded into species whose Mr was close to that of HN found in acidic brain extract. In brain or nerve neutral pH extracts, both HN-like antigen and HN were present. The high Mr of the secreted antigen, the homology in amino acid sequences between HN and N-terminal domain of PG-M/versican, in addition to a positive hybridization between Schwann cell RNAs and a probe obtained with primers derived from HN sequences also found in versican suggested that HN is closely related to the large proteoglycan PG-M/versican. The presence in Schwann cell extract of a HN mRNA whose Mr was compatible with the size expected for HN showed that HN may be directly secreted by cells and not only the consequence of a proteolytic cleavage. The similarity of HN with PG-M (V3) suggested that HN found in vivo could be the result of an alternative splicing of a single gene. We conclude that HN as other members of the PG-M/versican family is a marker of oligodendrocytes and Schwann cells in culture.

Animals↗
PubMed1998

Regulation of neuroprotective action of vasoactive intestinal peptide in the murine developing brain by protein kinase C and mitogen-activated protein kinase cascades: in vivo and in vitro studies.

Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white matter lesions mimicking periventricular leukomalacia, the most frequent brain lesion occurring in premature human babies. In this model, coinjection of vasoactive intestinal peptide prevents white matter lesions. In the present study, coadministration of ibotenate, vasoactive intestinal peptide, and selective transduction inhibitors showed that protein kinase C and mitogen-associated protein kinase pathways were critical for neuroprotection. In vivo and in vitro immunocytochemistry revealed that vasoactive intestinal peptide activated protein kinase C in astrocytes and neurons, and mitogen-associated protein kinase in neurons. In vitro neuronal transduction activation was indirect and required medium conditioned by astrocytes in which protein kinase C had been activated by vasoactive intestinal peptide. Although vasoactive intestinal peptide did not prevent the initial in vivo appearance of white matter lesion, it promoted a secondary repair of this lesion with axonal regrowth. Through protein kinase C activation, vasoactive intestinal peptide also prevented ibotenate-induced white matter astrocyte death. These data support the following hypothetical model: Vasoactive intestinal peptide activates protein kinase C in astrocytes, which promotes astrocytic survival and release of soluble factors; these released factors activate neuronal mitogen-associated protein kinase and protein kinase C, which will permit axonal regrowth.

Animals↗
PubMed1998

Enterovirus-associated haemophagocytic syndrome in a neonate.

A 3-d-old neonate presented with fever, hepatosplenomegaly, coagulopathy, thrombopenia and anaemia. Secondary haemophagocytic lymphohistiocytosis was suspected, as persistent cytopenias were associated with hypofibrinogenaemia, haemophagocytosis in bone marrow and decreased NK cell. There was no positive family lymphohistiocytosis history or parental consanguinity. Bacterial investigation proved negative. The diagnosis of enterovirus maternofoetal infection was carried out. The infant's condition improved with symptomatic therapy from day 7. Follow up at 1 y was normal without relapse. This is the first report of a neonatal enteroviral infection that was responsible for excessive macrophage activation.

Enterovirus Infections↗
PubMed1997

Caffeine-induced disturbances of early neurogenesis in whole mouse embryo cultures.

In toto mouse embryos were cultivated at embryonic day 8.5 for 26 h with 105, 310 or 620 microM caffeine; 105-310 microM correspond to concentrations transferred by the placenta of heavy caffeine consumers. Failure of neural tube closure, excessive proliferation of neuroepithelial cells and premature evagination of telencephalic vesicles were present in 50% of treated embryos. When reaching the embryonic neural tube before neuronal migration, caffeine regionally modifies the schedule and/or rate of neural cell proliferation.

Abnormalities, Drug-Induced↗
PubMed1997

Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain.

Excitotoxic damage may be a critical factor in the formation of brain lesions associated with cerebral palsy. When injected at birth, the glutamatergic analog ibotenate induces mouse brain lesions that strikingly mimic human microgyria. When ibotenate is injected at postnatal day 5, it produces transcortical necrosis and white matter cysts that mimic human perinatal hypoxic-like lesions. Vasoactive intestinal peptide (VIP) has potent growth-related actions and neuroprotective properties that influence mitosis and neuronal survival in culture. The goal of this study was to assess the protective role of VIP against excitotoxic lesions induced by ibotenate in developing mouse brain. VIP cotreatment reduced ibotenate-induced microgyric-like cortical lesions and white matter cysts by up to 77 and 85%, respectively. VIP protective effects were reproduced by a peptide derived from activity-dependent neurotrophic factor (ADNF), a trophic factor released by VIP-stimulated astrocytes, and by stearyl norleucine VIP, a specific VIP agonist that does not activate adenylate cyclase. Neither forskolin, an adenylate cyclase activator, nor pituitary adenylate cyclase-activating peptide, provided VIP-like protection. VIP and neurotrophic analogs, acting through a cAMP-independent mechanism and inducing ADNF release, could represent new avenues in the understanding and prevention of human cerebral palsy.

Animals↗
PubMed1997

Prognostic value of neonatal electroencephalography in premature newborns less than 33 weeks of gestational age.

In a prospective study of 417 premature neonates born before 33 weeks' gestational age, neonatal tracings were reviewed to evaluate the use of EEG in prognosis of neurological injuries. The population was divided into two groups: Group 1, infants who died before the age of 1, and Group 2, survivors in which two categories of motor development were considered. Category A, were abnormal, and Category B, were always normal. Positive rolandic sharp waves (PRSW), which reflect white matter injury, occurred equally in both groups, indicating a similar incidence of white matter damage in Groups 1 and 2. In Group 2, there was a significant correlation of PRSW with developmental motor sequelae (Category A). A frequency of PRSW above 2/min (suggesting more severe periventricular white matter injury) and seizures were significantly more prevalent in Group 1 than in Group 2 and in Category A of Group 2 than in Category B. Background abnormalities occurred equally in both subgroups of extremely premature infants (< or = 28 weeks' gestation) they were significantly more numerous in the subgroup of very premature infants (between 28 and 33 weeks' gestation) who died, than in the subgroup of very premature infants who survived. This study shows the potential utility of using neonatal EEG in association with transfontanellar ultrasonography in anticipating the neurological development of very (> 28 weeks' gestation) and extremely (< or = 28 weeks' gestation) premature newborns.

Asphyxia↗