Cerebral white matter damage in the preterm infant: pathophysiology and risk factors |
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Institution: | 1. Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan;2. Center for Medical Science, International University of Health and Welfare, 2600-1 Kita-Kanemaru, Ohtawara, Tochigi 324-8501, Japan;12. Cancer Epidemiology Unit, University of Turin, Department of Medical Sciences, Torino, Italy |
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Abstract: | Based on clinical, epidemiologic, and experimental studies, the aetiology of white matter damage, specifically periventricular leukomalacia (PVL), is multifactorial and involves pre- and perinatal factors possibly including genetic factors, hypoxic-ischaemic insults, infection, excess cytokines, free radical production, increased excitatory amino acid release, and trophic factor deficiencies. The article summarizes research findings about the aetiology of white matter damage and cerebral palsy in preterm infants. The information is organized according to specific antecedents, for which we present epidemiological and neurobiological data. The most important prenatal factor appears to be intrauterine infection. We discuss the evidence supporting the hypothesis that the foetal inflammatory response contributes to neonatal brain injury and later developmental disability. We recently established an animal model of excitotoxic lesions in the developing mouse brain. Brain damage was induced by intra-cortical injections of ibotenate, a glutamatergic agonist. When administered on post-natal day 5 ibotenate induced the formation of white matter cysts. Our animal model could be used to further explore the mechanisms involved in the formation of PVL. Potentially preventive strategies will be discussed. |
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