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Epidemiological studies have shown a strong association between perinatal infection / inflammation and brain damage in the newborn and/or neurological handicap in survivors. Experimental studies have allowed to show a causal effect of infection / inflammation on perinatal brain damage.
Infection / inflammatory factors can induce brain damage by themselves. Accordingly, injection of E Coli to pregnant rabbits induces periventricular white matter cysts and widespread white matter cell death, mimicking brain damage observed in preterm infants. In addition, injection of Ureaplasma Parvum to pregnant mice induces myelin defects and loss of interneurons in the offspring. Similarly, injection of LPS to pregnant rats induces transient central inflammation and myelination defects in the offspring.
Alternatively, in the so-called multiple hit hypothesis, infection / inflammation can act as predisposing factors making the brain more susceptible to a second stress (sensitization process). Indeed, injection of low doses LPS to developing rats makes the newborn brain significantly more susceptible to hypoxic-ischemic insult. Similarly, injection of interleukin-1-beta to newborn mice or rats makes the brain much more sensitive to an excitotoxic insult. Current studies are evaluating the time window during which sensitization of the brain will persist after exposure to inflammatory factors in the perinatal period. In addition, the mechanisms by which sensitization is working are not yet fully undertsood but could include changes in gene transcription and modifications of glutamate receptor activity.
Epidemiological data also suggest that perinatal exposure to inflammatory factors could predispose to long term diseases including psychiatric disorders. This could be particularly the case for preterm infants whose brain could be more sensitive to environmental factors when compared to full term infants. In this context, exposure of newborn mice to low doses of interleukin-1-beta during the neonatal period has been recently shown to disrupt oligodendrocyte maturation, myelin formation and axonal development. These white matetr abnormalities are moderate during the developmental period but do persist until adulthood. They lead to permanent deficiencies in behavioral tests without detectable effects on motor functions. The underlying molecular mechanisms include alterations of the transcription of genes implicated in oligodendrogenesis, myelin formation and axonal maturation.
Altogether, these clinical and experimental data strongly support the hypothesis that exposure to infection / inflammation during pregnancy or the eprinatal period is deleterious for the brain. This can lead to the appearance of perinatal brain damage that can lead to long term neurological and cognitive disabilities. In addition, some data also suggest that the perinatal exposure to inflammatory factors can alter the programs of brain development.

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