title: Models of fetal brain injury, intrauterine inflammation, and preterm birth.
abstract: Intrauterine infection and inflammation are known risk factors for brain damage in the neonate irrespective of the gestational age. Infection-induced maternal immune activation leads to a fetal inflammatory response mediated by cytokines that has been implicated in the development of not only periventricular leukomalacia and cerebral palsy but also a spectrum of neurodevelopmental disorders such as autism and schizophrenia (Behav Brain Res 2009; 204:313, Ann Neurol 2005; 57:67, Am J Obstet Gynecol 2000; 182:675). A common link among the neurobehavioral disorders associated with intrauterine inflammation appears to be the evidence for immune dysregulation in the developing brain (Behav Brain Res 2009; 204:313). The timing of the immune challenge with respect to the gestational age and neurologic development of the fetus may be crucial in the elicited response (J Neurosci 2006; 26:4752). Studies involving animal models of maternal inflammation serve a key role in elucidation of mechanisms involved in fetal brain injury associated with exposure to the maternal milieu. These animal models have been shown to result in fetal microglial activation, neurotoxicity as well motor deficits and behavioral abnormalities in the offspring (J Neurosci 2006; 26:4752, J Neurosci Res 2010; 88:172, Am J Obstet Gynecol 2009; 201:279, Am J Obstet Gynecol 2008; 199:651). A better understanding of the mechanisms of perinatal brain injury will allow discoveries of novel neuroprotective agents, better outcomes following preterm birth and stratification of fetuses and neonates for therapies in cases of preterm birth, preterm premature rupture of membranes, and chorioamnionitis.
authors.affiliation: Department of Gynecology, Johns Hopkins University, Baltimore, MD 20905, USA. iburd1@jhmi.edu
authors.forename: Irina
authors.initials: I
authors.lastname: Burd
authors.forename: Bindu
authors.initials: B
authors.lastname: Balakrishnan
authors.forename: Sujatha
authors.initials: S
authors.lastname: Kannan
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D001930:Brain Injuries / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007239:Infections / Q000188:drug therapy / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D047928:Premature Birth / Q000276:immunology* / Q000473:pathology; D014599:Uterus / Q000276:immunology / Q000473:pathology*
chemical_list: D016207:Cytokines