Interneuron Development Is Disrupted in Preterm Brains With Diffuse White Matter Injury: Observations in Mouse and Human

摘要: Preterm brain injury, occurring in approximately 30% of infants born <32 weeks gestational age, is associated with an increased risk neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity (ADHD). The mechanism gray matter injury preterm children unclear likely to be multifactorial; however, inflammation, a high predictor poor outcome infants, has been disrupted interneuron maturation number animal models. Interneurons are important for regulating normal development, disruption the downstream effects this, implicated etiology disorders. Here, we utilize postmortem tissue from human cases or without diffuse white (WMI; PMA range: 23+2 28+1 non-WMI group, 26+6 30+0 WMI p = 0.002) model inflammation-induced (i.p. IL-1β, b.d., 10 μg/kg/injection male CD1 mice P1-5). Data show deficits numbers cortex delayed growth neuronal arbors at this early stage development. In mouse, significant reduction parvalbumin-positive interneurons was observed postnatal day (P) 10. This decrease parvalbumin neuron largely rectified by P40, though there significantly smaller positive cells perineuronal nets upper cortical layers. Together, these data suggest that inflammation may contributor specific matter. represent potential target therapy reduce incidence and/or severity disorders infants.