N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

Abstract

Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development.

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism

“…Social behavior is regulated by specific brain areas, and abnormal fetal brain development has been reported in prenatally LPS-exposed mice [ 27 ]. Moreover, previous studies have drawn inconsistent conclusions regarding changes in embryonic cortical thickness and lamination in MIA models [ 17 , 33 ].…”

“…Images were observed and captured with a BX63 Olympus microscope. The measurements of the dorsal and lateral neocortex were based on the previous report [ 27 ]. Total neocortical thickness was measured along a line orthogonal to the superficial pia and lateral ventricular surfaces, as the red line shown in Fig.…”

N-acetylcysteine inhibits bacterial lipopeptide-mediated neutrophil transmigration through the choroid plexus in the developing brain

“…NAC has been shown to ameliorate postnatal or laterlife neurological outcome in different models of perinatal diseases, when administrated to the mother before birth or postnatally to the pups [1,4,7,33,62]. It has been the object of a positive clinical trial in the context of chorioamnionitis [26].…”

Effects of Atypical Neurotoxins on the Developing Fetal Brain

“…The findings in experimental models of maternal infection manifest the role of inflammatory response in the alteration of fetal neuronal morphology [97], astrocytosis, ventriculomegaly, changes in oligodendrocyte precursors [98], reduction of oligodendrocyte number, hypomyelination of brain [99] and a decrease of dopaminergic and serotoninergic neurons in the offspring [100], all of which are capable of leading to brain formative deficits. Indeed, maternal infection induces changes in brain developmental events, including neurogenesis, myelination, synaptogenesis as well as cell migration [101,102]. Neuroinflammation has been reported to be highly associated with numbers of neurological and pathological diseases, such as cerebral palsy [94], schizophrenia [95], and autism spectrum disorders [96].…”