ORCID Profile
0000-0002-0301-2053
Current Organisations
Normandie Université
,
Centre Hospitalier Universitaire de Caen Pôle Femme-Enfant
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Publisher: Wiley
Date: 27-07-2011
DOI: 10.1002/ANA.22489
Abstract: Perinatal inflammation is a major risk factor for neurological deficits in preterm infants. Several experimental studies have shown that systemic inflammation can alter the programming of the developing brain. However, these studies do not offer detailed pathophysiological mechanisms, and they rely on relatively severe infectious or inflammatory stimuli that most likely do not reflect the levels of systemic inflammation observed in many human preterm infants. The goal of the present study was to test the hypothesis that moderate systemic inflammation is sufficient to alter white matter development. Newborn mice received twice-daily intraperitoneal injections of interleukin-1β (IL-1β) over 5 days and were studied for myelination, oligodendrogenesis, and behavior and with magnetic resonance imaging (MRI). Mice exposed to IL-1β had a long-lasting myelination defect that was characterized by an increased number of nonmyelinated axons. They also displayed a reduction of the diameter of the myelinated axons. In addition, IL-1β induced a significant reduction of the density of myelinating oligodendrocytes accompanied by an increased density of oligodendrocyte progenitors, suggesting a partial blockade in the oligodendrocyte maturation process. Accordingly, IL-1β disrupted the coordinated expression of several transcription factors known to control oligodendrocyte maturation. These cellular and molecular abnormalities were correlated with a reduced white matter fractional anisotropy on diffusion tensor imaging and with memory deficits. Moderate perinatal systemic inflammation alters the developmental program of the white matter. This insult induces a long-lasting myelination deficit accompanied by cognitive defects and MRI abnormalities, further supporting the clinical relevance of the present data.
Publisher: Wiley
Date: 30-08-2017
DOI: 10.1002/GLIA.23212
Publisher: Springer Science and Business Media LLC
Date: 15-12-2011
DOI: 10.1038/PR.2011.3
Abstract: To implement neuroprotective strategies in newborns, sensitive and specific biomarkers are needed for identifying those who are at risk for brain damage. We evaluated the effectiveness of matrix metalloproteinases (MMPs) and their naturally occurring tissue inhibitors of metalloproteinases (TIMPs) in predicting neonatal encephalopathy (NE) damage in newborns. Plasma MMP-9 and TIMP-1 levels were upregulated as early as 1 h after the HI insult but not did not show such elevations after other types of injury (ibotenate-induced excitotoxicity, hypoxia, lipopolysaccharide-induced inflammation), and brain levels reflected this increase soon thereafter. We confirmed these results by carrying out plasma MMP-9 and TIMP-1 measurements in human newborns with NE. In these infants, protein levels of MMP-9 and TIMP-1 were found to be elevated during a short window up to 6 h after birth. This feature is particularly useful in identifying newborns in need of neuroprotection. A second peak observed 72 h after birth is possibly related to the second phase of energy failure after a HI insult. Our data, although preliminary, support the use of MMP-9 and TIMP-1 as early biomarkers for the presence and extent of perinatal brain injury in human term newborns. We first used a mouse model of neonatal HI injury to explore mechanistic aspects such as the time course of these markers after the hypoxia-ischemia event, and the correlation between the levels of these candidate markers in brain and plasma.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.ARCPED.2012.06.013
Abstract: Perinatal inflammation can lead to fetal/neonatal inflammatory syndrome, a risk factor for brain lesions, especially in the white matter. Perinatal inflammation is associated with increased incidence of cerebral palsy in humans and animal models and there is a strong relationship with increased incidence of autism and schizophrenia in humans. Perinatal inflammation causes acute microglial and astroglial activation, blood-brain barrier dysfunction, and disrupts oligodendrocyte maturation leading to hypomyelination. Inflammation also sensitizes the brain to additional perinatal insults, including hypoxia-ischemia. Furthermore, long after the primary cause of inflammation has resolved, gliosis may also persist and predispose to neurodegenerative diseases including Alzheimer's and Parkinson's disease, but this relation is still hypothetical. Finding of acute and chronic changes in brain structure and function due to perinatal inflammation highlights the need for treatments. As gliosis appears to be involved in the acute and chronic effects of perinatal inflammation, modulating the glial phenotype may be an effective strategy to prevent damage to the brain.
Location: United Kingdom of Great Britain and Northern Ireland
Location: France
No related grants have been discovered for Geraldine Favrais.