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Fetal inflammation is associated with persistent systemic and hippocampal inflammation and dysregulation of hippocampal glutamatergic homeostasis.


ABSTRACT: BACKGROUND:Inflammation is a major cause of preterm birth and often results in a fetal inflammatory response syndrome (FIRS). Preterm infants with FIRS have a higher childhood incidence of neurodevelopmental disability than preterm infants without FIRS. The mechanisms connecting FIRS to neurodevelopmental disability in formerly preterm infants are not fully understood, but the effect on premature gray matter may have an important role. METHODS:Fetal rats were exposed to intra-amniotic (i.a.) LPS 2 days prior to birth to model FIRS. On postnatal day 7, expression of inflammatory mediators was measured in the liver, lung, and brain. Activation of microglia and expression of glutamatergic receptor subunits and transporters were measured in the hippocampus and cortex. RESULTS:LPS caused persistent systemic inflammatory mediators gene expression. In the brain, there was corresponding activation of microglia in the hippocampus and cortex. Expression of inflammatory mediators persisted in the hippocampus, but not the cortex, and was associated with altered glutamatergic receptor subunits and transporters. CONCLUSION:Hippocampal inflammation and dysregulation of glutamate metabolism persisted well into the postnatal period following i.a. LPS. Poor neurodevelopmental outcomes after FIRS in preterm infants may result in part through glutamatergically driven gray matter injury to the neonatal hippocampus.

SUBMITTER: Gisslen T 

PROVIDER: S-EPMC6435426 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Fetal inflammation is associated with persistent systemic and hippocampal inflammation and dysregulation of hippocampal glutamatergic homeostasis.

Gisslen Tate T   Singh Garima G   Georgieff Michael K MK  

Pediatric research 20190211 5


<h4>Background</h4>Inflammation is a major cause of preterm birth and often results in a fetal inflammatory response syndrome (FIRS). Preterm infants with FIRS have a higher childhood incidence of neurodevelopmental disability than preterm infants without FIRS. The mechanisms connecting FIRS to neurodevelopmental disability in formerly preterm infants are not fully understood, but the effect on premature gray matter may have an important role.<h4>Methods</h4>Fetal rats were exposed to intra-amni  ...[more]

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2023-07-11 | GSE209806 | GEO