Glial activation in white matter following ischemia in the neonatal P7 rat brain

This study examines cell death and proliferation in the white matter after neonatal stroke. In post-natal day 7 injured rat, there was a marked reduction in myelin basic protein (MBP) immunostaining mainly corresponding to numerous pyknotic immature oligodendrocytes and TUNEL-positive astrocytes in the ipsilateral external capsule. In contrast, a substantial restoration of MBP, as indicated by the MBP ratio of left-toright, occurred in the cingulum at 48 (1.27 +- 0.12) and 72 (1.30 +- 0.18, p<0.05) hours of recovery as compared to age-matched controls (1.03 +- 0.14). Ki-67 immunostaining revealed a first peak of newly-generated cells in the dorsolateral hippocampal subventricular zone and cingulum at 72 hours after reperfusion. Double immunofluorescence revealed that most of the Ki-67-positive cells were astrocytes at 48 hours and NG2 pre-oligodendrocytes at 72 hours of recovery. Microglia infiltration occurs over several days in the cingulum and a huge quantity of macrophages reached the subcortical white matter where they engulfed immature oligodendrocytes. The overall results suggest that the persistent activation of microglia involves a chronic component of immunoinflammation, which overwhelms repair processes and contributes to cystic growth in the developing brain.Comment: 30 page

Melatonin Promotes Oligodendroglial Maturation of Injured White Matter in Neonatal Rats

OBJECTIVE:To investigate the effects of melatonin treatment in a rat model of white matter damage (WMD) in the developing brain. Additionally, we aim to delineate the cellular mechanisms of melatonin effect on the oligodendroglial cell lineage. METHODS:A unilateral ligation of the uterine artery in pregnant rat at the embryonic day 17 induces fetal hypoxia and subsequent growth restriction (GR) in neonatal pups. GR and control pups received a daily intra-peritoneal injection of melatonin from birth to post-natal day (P) 3. RESULTS:Melatonin administration was associated with a dramatic decrease in microglial activation and astroglial reaction compared to untreated GR pups. At P14, melatonin prevented white matter myelination defects with an increased number of mature oligodendrocytes (APC-immunoreactive) in treated GR pups. Conversely, melatonin was not found to be associated with an increased density of total oligodendrocytes (Olig2-immunoreactive), suggesting that melatonin is able to promote oligodendrocyte maturation but not proliferation. These effects appear to be melatonin-receptor dependent and were reproduced in vitro. INTERPRETATION:These data suggest that melatonin has a strong protective effect on developing damaged white matter through decreased microglial activation and oligodendroglial maturation leading to a normalization of the myelination process. Consequently, melatonin should be a considered as an effective neuroprotective candidate not only in perinatal brain damage but also in inflammatory and demyelinating diseases observed in adults

Facteurs inflammatoires dans les lésions ischémiques cérébrales périnatales (un modèle chez le rat)

Nous nous sommes focalisés sur l étude de la substance blanche et les mastocytes cérébraux (M) dans un modèle d'ischémie-reperfusion chez le raton P7 reproduisant les lésions cérébrales de l'encéphalopathie hypoxique-ischémique du nouveau-né humain proche du terme. Il existe une dégénérescence des oligodendrocytes matures et immatures, des astrocytes entre J0 et J3 après ischémie dans la capsule externe.Une prolifération cellulaire dans les 2 hémisphères concerne essentiellement les astrocytes et les préoligodendrocytes, à 48h post-ischémie. A 7 j post-ischémie, peu de cellules Ki67-GFAP positives sont mises en évidence dans la zone sous-ventriculaire ce qui pourrait correspondre à une éventuelle oligodendrogenèse. Une augmentation significative de la microglie amoeboïde est également observée entre 24 et 72 h post-ischémie, suggèrant une interférence avec la maturation des préoligodendrocytes, empêchant ainsi la remyélinisation. Les cellules microgliales, grâce à leur capacité à synthétiser des composants cytotoxiques, pourraient participer à l induction de la mort cellulaire secondaire. Nous avons mis en évidence une accumulation d histamine (H) dans les neurones et une augmentation importante du nombre de M dans la piemère. La détection précoce de l immunoréactivité histaminergique dans la paroi des vaisseaux sanguins est un argument pour une origine périphérique de l H qui pénètre dans le cerveau durant la phase de reperfusion, suggérant une rupture précoce de la barrière hémato-encéphalique. L autre source est représentée par les M. Ces phénomènes immuno-inflammatoires pourraient contribuer à la dégénérescence neuronale induite par l ischémie.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Probing the Impact of Prematurity on Segmentation Abilities in the Context of Bilingualism

Infants born prematurely are at a high risk of developing linguistic deficits. In the current study, we compare how full-term and healthy preterm infants without neuro-sensorial impairments segment words from fluent speech, an ability crucial for lexical acquisition. While early word segmentation abilities have been found in monolingual infants, we test here whether it is also the case for French-dominant bilingual infants with varying non-dominant languages. These bilingual infants were tested on their ability to segment monosyllabic French words from French sentences at 6 months of (postnatal) age, an age at which both full-term and preterm monolinguals are able to segment these words. Our results establish the existence of segmentation skills in these infants, with no significant difference in performance between the two maturation groups. Correlation analyses failed to find effects of gestational age in the preterm group, as well as effects of the language dominance within the bilingual groups. These findings indicate that monosyllabic word segmentation, which has been found to emerge by 4 months in monolingual French-learning infants, is a robust ability acquired at an early age even in the context of bilingualism and prematurity. Future studies should further probe segmentation abilities in more extreme conditions, such as in bilinguals tested in their non-dominant language, in preterm infants with medical issues, or testing the segmentation of more complex word structures

Neurocognitive outcomes at age 5 years after prophylactic hydrocortisone in infants born extremely preterm

Aim: To assess the 5-year neurocognitive outcomes of children born extremely preterm exposed to prophylactic hydrocortisone to improve survival without bronchopulmonary dysplasia. Method: This was a prespecified secondary analysis of the PREMILOC clinical trial (trial registration: EudraCT no. 2007-002041-20, NCT00623740). The primary outcome was full-scale IQ based on the Wechsler Preschool and Primary Scale of Intelligence. Results: Among 109 surviving children recruited at the Robert Debré Children's Hospital, Paris, outcome data were available for 42 out of 56 infants (75%) in the group treated with hydrocortisone and 41 out of 53 (77%) in the placebo group. Mean scores were not significantly different between the two groups on full-scale IQ (hydrocortisone: 91.9 [SD = 13.9], placebo: 86.3 [SD = 15.4]; mean difference = 5.7, 95% confidence interval [CI] = -1.0 to 12.3, p = 0.10); however, working memory and retention ability were significantly better in the group treated with hydrocortisone. In a multivariate logistic regression including potential confounding variables, hydrocortisone treatment was significantly associated with a greater chance to survive at 5 years of age with a full-scale IQ equal to or greater than 90 compared to placebo (adjusted odds ratio = 4.26, 95% CI = 1.47-12.36, p = 0.008). Interpretation: This exploratory analysis provides reassuring data regarding the long-term neurodevelopmental safety of prophylactic hydrocortisone in infants born extremely preterm.</p

Two-year neurodevelopmental outcomes of extremely preterm infants treated with early hydrocortisone: treatment effect according to gestational age at birth

To determine whether early hydrocortisone treatment in extremely preterm infants affects neurodevelopmental outcomes at 2 years of age according to gestational age at birth

Neuronal damage in the preterm baboon:impact of the mode of ventilatory support

We evaluated the impact of randomized ventilatory strategies on specific neuronal populations of the cerebral cortex of preterm baboons. In the first series, baboons (n = 5) were delivered at 125 days of gestation (dg; term = 185 days) and exposed to 14 days of positive pressure ventilation (PPV) and compared to 140 dg controls (n = 6). In the second series, baboons were delivered at 125 dg and ventilated by either (i) PPV for 1 day followed by 27 days of nasal continuous positive airway pressure (early [EnCPAP]; n = 6) or (ii) PPV for 5 days followed by 23 days of CPAP (delayed [DnCPAP]; n = 4). Gestational controls were delivered at 153 dg (n = 3). The density of immunoreactive neurons for calretinin and somatostatin was assessed in the primary and secondary visual cortices, cingulate and parietal cortices and subiculum in paraffin sections. Compared to gestational controls, PPV for 14 days resulted in a reduction in the density of calretinin+ cells in the visual cortex (areas 17 and 18) but not in the other cortical areas. No effect of PPV was observed on somatostatin+ cells. DnCPAP, but not EnCPAP, was associated with a reduction in the density of calretinin and somatostatin+ cells in the visual cortical areas but not in the other cortical areas compared to gestational controls. Taken together, these data demonstrate that ventilatory strategies involving > 5 days of PPV have a regionally selective impact on cortical neuronal subpopulations within the visual area but not in areas of association cortex in a non-human primate model of prematurity

Etude de l'histamine au cours du développement des lesions consecutives à une ischémie cérébrale néonatale

International audienc

Early-onset neonatal sepsis in the Paris area: a population-based surveillance study from 2019 to 2021

International audienceBackground Early-onset neonatal sepsis (EOS) is a rare condition but an important cause of severe morbidity and mortality in neonates. Methods This is a prospective observational study in neonates born at ≥34 weeks of gestation (WG). The primary endpoint was EOS, defined by isolation of pathogenic species from blood culture and/or cerebrospinal fluid culture within 72 hours after birth. Data on EOS were collected exhaustively from all maternity wards in Paris area (April 2019–March 2021). Results 108 EOS were recorded (annual incidence, 0.32 per 1000 live births; 95% CI 0.26 to 0.38). In term infants, the most frequent pathogens were group B Streptococcus (GBS) (n=47) and Escherichia coli (n=20); in late preterm infants, the most frequent pathogens were E. coli (n=15) and GBS (n=7). Fifteen meningitis cases were diagnosed. Five E. coli strains (14%) were resistant to both amoxicillin and gentamicin, which is an empiric treatment for EOS. Of the 54 infants with GBS infections, 35 were born from mothers with negative GBS prepartum screening test and 8 from mothers with no screening. Two deaths were reported, both in term infants ( Proteus mirabilis and E. coli ). Conclusion In neonates ≥34 WG born in the Paris area, GBS was twice as frequent as E. coli in term infants. EOS was six times more frequent in late preterm than in term infants and was due to E. coli in 60% of cases. Prevention of GBS EOS and empiric antibiotic treatment of EOS could be improved