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Biomedical subjects

S Marret

Publications and source records attributed to S Marret.

68 records · Page 4Linked to original sources
PubMed1996

Developmental spectrum of the excitotoxic cascade induced by ibotenate: a model of hypoxic insults in fetuses and neonates.

Ibotenate, a glutamatergic agonist, was used to study the spectrum of excitoxic disturbances at different ages of cerebral development. Cultures of whole mouse embryo were submitted to ibotenate at E8 for 20 h: during the phase of early premigratory differentiation: ibotenate did not induce any detectable histological lesion. During migration of supragranular neurons, newborn hamsters intracerebrally injected at PO with ibotenate display neuronal migration disorders graded from nodular heterotopias to extensive laminar heterotopias mimicking some aspects of lissencephalic and double-cortex syndromes. After completion of neuronal layer V, PO mice injected with ibotenate exhibit laminar neuronal depopulation of layer V-VIa mimicking human microgyria. At P5 in mouse, after completion of neuronal migration of the cortical plate, ibotenate induces neuronal loss in all cortical layers and the formation of porencephalic cysts. This study emphasizes the dramatic role played by glutamate in brain development, in the occurrence of neuronal migration disorders in the cortex, and in grey and white matter damage.

Animals↗
PubMed1995

CNS myelinogenesis in vitro: time course and pattern of rat oligodendrocyte development.

Oligodendrocyte precursor cells that develop into myelin-forming cells of the central nervous system (CNS) were cultured from newborn rat brain to study how they proliferate and differentiate in normal conditioning medium, and their cell development was characterized by scanning electron microscopy (SEM) observation and immunocytochemical studies. We have identified A2B5-negative pre-O2A progenitor cells (so-called "type-1" oligodendrocytes) in the secondary cultures on the astrocyte feeder layer. These cells are very small (diameter: 3.5 microns), round, and glossy, and develop into the process-bearing O2A progenitor cells (called "type-2" oligodendrocytes), which also express myelin basic protein (MBP) both in the cell body and in their cell processes. Finally, they develop into mature oligodendrocytes (called "type-3" oligodendrocytes). After MBP expression is elicited in these cells and MBP accumulates in the cell process in the area in contact with the axon, these cells are capable of forming the myelin sheath. Therefore, we examined the mechanism of myelin-sheath formation of "type-3" oligodendrocytes using video time-lapse movies, and demonstrated that these cells initially sent out processes to search for axons several times before the onset of myelination. Then thick filopodia extended towards the axon, and at the same time, the axonal part of neuron moved forward. Finally the ruffling lamellipodial parts wrapped up the axon similarly to a transverse wave with the secured thick filopodial process on the axon acting as scaffolding. These results suggest that our experimental systems are useful in studying normal oligodendrocyte development and their cellular biochemistry, as well as investigating the mechanism of myelin formation by oligodendrocytes.

Animals↗
PubMed1995

Effect of ibotenate on brain development: an excitotoxic mouse model of microgyria and posthypoxic-like lesions.

Ibotenate, a glutamatergic agonist, was injected in developing mouse neopallium. When injected at the time of completion of supragranular neuronal migration (P0) ibotenate induces complete neuronal depopulation of layers V-VI and an abnormal sulcation of the overlying supragranular layers. Injected after completion of migration (P5-P10) ibotenate produces severe neuronal loss in layers II, III, IV, V, and VI. After exposure to ibotenate between P0 and P5, surviving neurons have the ability to resume their migration, inducing an abnormal neocortical pattern. Periventricular white matter lesions are observed after ibotenate injection at P2-P10, with a peak of occurrence at P5. Both gray and white matter damage are prevented by DL-2-amino-7-phosphonoheptanoic acid, an N-methyl-D-aspartate receptor antagonist, but not by L (+)-2-amino-3-phosphonopropionic acid, a metabotropic glutamate receptor antagonist. The microtubule-associated type 2 protein, a dendritic marker, is absent in all ibotenate lesions, which reflects the developmental impairment of the dendritic phase. These staged lesions of the gray and white matter disclose a developmental sequence of excitotoxin-affected events starting with the selective and layered sensitivity of postmigratory neocortical neurons and continuing in the white matter with the astroglial maturation and the axonal growth. They faithfully mimic microgyrias, focal cortico-subcortical dysplasias, porencephalic cysts, and white matter damage observed in human perinatal hypoxic/ischemic lesions. This mouse model provides tools for investigating excitotoxic influences on neural development at the various stages and for identifying protective substances against excitotoxicity from hypoxic and from nonhypoxic origins.

2-Amino-5-phosphonovalerate↗
PubMed1995

Prevention by magnesium of excitotoxic neuronal death in the developing brain: an animal model for clinical intervention studies.

Excitotoxic disturbances during brain development were studied in the mouse using intracerebral injections of ibotenate, a glutamatergic agonist of the N-methyl-D-aspartate (NMDA) complex receptor, to analyse the protective effect of a systemic bolus of MgSO4, a non-competitive antagonist of the NMDA ionophore-complex receptor. MgSO4 did not prevent microgyia, induced by ibotenate when injected at P0 immediately after the post-migratory settlement of layer V, but did prevent ulegyrias, porencephalic cysts, and other cortical and cortical-subcortical hypoxic-like lesions arising after completion of the neocortical cyto-architectonic development at P5. Protection was optimal in 80 per cent of mice at 600mg/kg, with no mortality due to MgSO4; thereafter mortality increased with dosage. The protective effect appears after the developmental acquisition of two properties of the excitotoxic cascade, namely the coupling of the massive calcium influx with NMDA-receptor overstimulation and the predominance of magnesium-obliterable calcium channels. This animal model supports the clinical intervention studies with magnesium in hypoxias/perfusion failures and has implications for their design. If maturation of the excitotoxic cascade follows the same sequence in humans, protection is probably low before 26 weeks of gestational age.

Animals↗
PubMed1994

Expression and effects of hyaluronan and of the hyaluronan-binding protein hyaluronectin in newborn rat brain glial cell cultures.

Hyaluronan (HA) is a polymerized nonsulfated extracellular matrix glycosaminoglycan that may be involved in brain development. We have tested the expression of HA and the HA-binding protein hyaluronectin (HN) in glial cell cultures from newborn rat brain. HA was secreted into the culture medium by type 1 astrocytes in the first stages of the primary cultures. The secretion was high during cell proliferation, reached a maximum when they were confluent, and then decreased. HA was not secreted at a detectable level by total O-2A lineage cell-enriched cultures. HA labeled small O-2A progenitor cells (GFA-, A2B5+, HA+), small O-2A progenitorlike (GFA-, A2B5-, HA+) cells, and type 2 astrocytes (GFA+, A2B5+, HA+), but not mature oligodendrocytes (Galc+, HA-). In contrast to HA, hyaluronectin labeled oligodendrocyte membranes (i.e., more mature cells) from day 8. A2B5+ GFA- cells were found to be either HA+ or HN+ at days 7-9, suggesting intermediary stages. The addition of HA to primary cultures and to O-2A progenitor-enriched cultures decreased significantly the increase in the number of O-2A progenitors, of mature (Galc+) oligodendrocytes proportionally to the decrease of the O-2A progenitor number, and of BrdU+ cells, suggesting that HA acts (directly or indirectly) on O-2A cell proliferation. This effect, which was seen for concentrations as low as 0.1 micrograms/ml, was HA specific and was not observed with other glycosaminoglycans. When primary cultures were performed in the presence of hyaluronidase-digested or HA-depleted (by passage on a HN column) fetal calf serum, the total number of O-2A lineage cells was dramatically increased (100%, p < 10(-4)) in comparison with control cultures in standard fetal calf serum. Platelet-derived growth factor increased the total number of O-2A lineage cells and of (Galc+) oligodendrocytes. This effect was opposed by HA dose dependently. The effect of HA was significantly inhibited by HN (30%, p < 10(-4)). HN had, however, no effect when it was added to culture in the presence of hyaluronidase in fetal calf serum, suggesting its effect was only due to its binding to HA. During cell maturation, HA disappears as HN appears. This and the fact that HA and PDGF have opposite effects suggest an effect of these factors, or of their balance, on myelination.

Animals↗
PubMed1993

Herpes simplex hepatitis with chronic cholestasis in a newborn.

In the case of the central nervous system or hepatic involvement, the prognosis of neonatal herpes simplex infection remains poor, despite antiviral drugs, presumably effective if given early. We report the case of a neonate with herpes simplex hepatitis, where the course of the illness was unusual with chronic, ultimately fatal, cholestasis. The treatment was not effective, because its administration was delayed, because of high infant C reactive protein level and the absence of clinical maternal genital infection, and because it was interrupted due to misleading information: clinical improvement, negative viral tests and raised herpes IgG antibody titer.

Cholestasis↗
PubMed1993

Caffeine decreases glial cell number and increases hyaluronan secretion in newborn rat brain cultures.

Newborn rat brain astrocytes (type 1 astrocytes, O-2A progenitor cells, and O-2A progenitor-derived cells, i.e. oligodendrocytes and type 2 astrocytes) were cultivated to investigate the effect of addition of caffeine to the culture medium on glial cell development and secretion of hyaluronan (hyaluronic acid, HA). HA is a glycosaminoglycan, secreted by type 1 astrocytes especially, which is a major component of the extracellular matrix of immature brain involved in morphogenesis and differentiation. Caffeine was added to the culture medium of primary glial cell cultures at concentrations of 102 microM (20 mg/L) or 255 microM (50 mg/L), considered therapeutic and toxic levels, respectively, in human newborns. HA was measured in the culture medium by immunoenzyme assay using sheep brain hyaluronectin, a glycoprotein that exhibits a strong affinity for HA, as probe. In primary glial cell cultures, 102 microM (20 mg/L) caffeine had no visible effect on cell number or on HA secretion. At 255 microM (50 mg/L), there was a significant reduction of cell number (i.e. type 1 astrocytes, O-2A progenitor cells, and progenitor-derived cells) and a significant increase of HA secretion per cell. These results suggest that caffeine at a high concentration in brain could have a prejudicial effect on the number of proliferating glial cells (astrocytes and oligodendrocytes) and on the composition of the extracellular matrix, which could affect myelination onset.

Animals↗
PubMed1992

Positive rolandic sharp waves in the EEG of the premature newborn: a five year prospective study.

In a prospective study of 301 premature newborn infants, neonatal tracings were done to evaluate the use of the electroencephalogram (EEG) and positive rolandic sharp waves (PRSW) in the diagnosis and prognosis of periventricular leucomalacia. Each infant had ultrasonographic studies and standardised neurological examinations at 1 year of age or later. Two hundred and eighty infants were followed up at 1 year. This study demonstrated that the absence of PRSW was correlated with a favourable motor development (98.2%) and confirmed the great value of PRSW in the diagnosis and the prognosis of periventricular leucomalacia. PRSW were sensitive (98%) and specific (84%) markers of developmental motor disability and were a sensitive (96%) marker of severe spastic diplegia. A frequency above 2/minute was a specific (92%) sign of severe spastic diplegia. Social and language developmental abnormalities were not correlated with the neonatal EEG.

Cerebral Hemorrhage↗
PubMed1989

[Positive rolandic sharp waves, periventricular ischemia and neurologic outcome. Prospective study in 66 premature infants].

A prospective study concerning 66 prematures born after 32 weeks of gestation showed a 33% incidence of positive rolandic sharp waves (PRSW) on EEGs. The results showed a good sensitivity (Se = 95%) and specificity (Sp = 93%) of PRSW for the diagnosis of periventricular ischemia with motor sequelae. A PRSW frequency higher than one per minute and its persistence on 2 successive EEGs constitutes an indication of severity of the lesions. This study emphasizes the necessity of several EEG recordings in prematures.

Brain Ischemia↗
PubMed1987

[Retrospective study of 25 sudden death in 25 infants hospitalized during the neonatal period].

During a 6 years period, 25 newborns admitted to a neonatal intensive care unit died suddenly in the first year of life. The risk of sudden death in this specific population is 5% and reaches 7.4% in the low birth weight population (less than or equal to 2,500 g). In 12 infants, the sudden death was partially explained; in 7 infants, the sudden death remained unexplained on the basis of clinical and necropsic findings; in 6 infants, the clinical data did not justify the sudden death but necropsies were not performed. A comparison with matched living control infants showed that there was a significant increase of minor malformations of the branchial arch system and that in the sudden infant death group, threatening premature labour was more frequent during the mothers' pregnancies.

Abnormalities, Multiple↗
PubMed1986

Positive rolandic sharp waves and periventricular leukomalacia in the newborn.

Four cases of periventricular ischemia without hemorrhage in premature infants are described in which positive rolandic sharp waves (PRSW) were predominant in the electroencephalogram (EEG). These findings suggest the relationship of PRSW to periventricular ischemia rather than to intraventricular hemorrhage, per se, as has been considered by most investigations in the past. These PRSW can provide an early indication of periventricular leukomalacia.

Electroencephalography↗
PubMedDate not supplied

Activity-dependent neurotrophic factor-14 requires protein kinase C and mitogen-associated protein kinase kinase activation to protect the developing mouse brain against excitotoxicity.

Activity-dependent neurotrophic factor (ADNF) is a newly identified compound that prevents in vitro neuronal death when present in fentomolar concentrations. ADNF-14, a 14 amino acid peptide derived from ADNF, has the same effects on growth as the parent molecule. However, the transduction pathways and target cells for these highly potent trophic factors are still unknown. We previously described a mouse model of excitotoxic lesions of the developing neocortex mimicking several hypoxic or hypoxic-like brain lesions observed in human fetuses and neonates. In this model, cotreatment with the excitotoxin ibotenate and ADNF-14 prevented both neuronal death in pups injected on the day of birth and white matter cystic lesions in pups treated 5 d after birth. In the present study, coadministration of ibotenate, ADNF-14, and selective transduction pathway inhibitors showed that activation of protein kinase C (PKC) and mitogen-associated protein kinase kinase was critical for neuroprotection. Immunocytochemistry revealed that ADNF-14 activated PKC and mitogen-associated protein kinase in cortical neurons on the day of birth and in white matter astrocytes on the fifth postnatal day. Taken in concert, these data identify PKC and mitogen-associated protein kinase pathways as critical to ADNF-14-induced neuroprotection of the developing brain against excitotoxic damage.

Animals↗