Effects of Lipopolysaccharide and Progesterone Exposures on Embryonic Cerebral Cortex Development in Mice.

Our objective was to determine if progesterone pretreatment could ameliorate the detrimental effects of lipopolysaccharide (LPS)-induced inflammation on cortical neurogenesis. Timed pregnant mouse dams (n = 8) were given intraperitoneal injections of progesterone (42 mg/kg) or vehicle on embryonic day 17.5. Two hours later, mice were given intraperitoneal LPS (140 µg/kg) or vehicle. Mice were sacrificed 16 hours later on embryonic day 18. Two-color immunofluorescence was performed with primary antibodies T-box transcription factor 2 (Tbr2), ionized calcium binding adapter molecule 1 (Iba1), cleaved caspase 3 (CC3), and 5-bromo-2'-deoxyuridine (BrdU). Cells were counted, and statistical analysis was determined using analysis of variance and Tukey-Kramer method. The Tbr2 intermediate neural progenitor cell density decreased after LPS exposure (P = .0022). Pre-exposure to progesterone statistically increased Tbr2 intermediate neural progenitors compared to LPS treatment alone and was similar to controls (P = .0022). After LPS exposure, microglia displayed an activated phenotype, and cell density was increased (P < .001). Cell death rates were low among study groups but was increased in LPS exposure groups compared to progesterone alone (P = .0015). Lipopolysaccharide-induced systemic inflammation reduces prenatal neurogenesis in mice. Pre-exposure with progesterone is associated with increased neurogenesis. Progesterone may protect the preterm brain from defects of neurogenesis induced by inflammation.

Maternal N-acetyl-cysteine (NAC) protects the rat fetal brain from inflammatory cytokine responses to lipopolysaccharide (LPS).

OBJECTIVE: Inflammatory cytokines, play a central role in the genesis of preterm parturition and fetal brain injury. Lipopolysaccharide (LPS) may activate cytokine pathways via induction of oxidative stress pathways. We hypothesized that enhanced maternal antioxidant activity may blunt fetal brain inflammatory responses to maternal LPS injection in pregnant rats. METHODS: Pregnant Sprague-Dawley rats at 18 and 20 days gestation received intraperitoneal (ip) LPS injection and pre- and post-treatment with the antioxidant N-acetyl-cysteine (NAC) or saline. Six hours after the LPS injection, rats were sacrificed, interleukin (IL)-6 and IL-10 mRNA expression in the fetal brains was determined by real time polymerase chain reaction. RESULTS: Maternal ip LPS induced significant increase in fetal brain IL-6 mRNA expression at E18 (3.1 ± 0.6 vs 1.0 ± 0.10 AU) and E20 (29.01 + 13.06 vs 0.95 + 0.05 AU; p < 0.05) compared to Control, only at E20 maternal LPS induced increase in fetal brain IL-10 compared to control. NAC administered prior to and after LPS significantly reduced fetal brain IL-6 at E18 and E20 and IL-10 at E20. CONCLUSION: Maternal NAC can protect the fetal brain from inflammatory cytokine responses to maternal LPS injection. These results suggest that NAC may potentially protect fetus from inflammation-associated brain injury and potential long term sequelae.

Impaired migration signaling in the hippocampus following prenatal hypoxia.

Prenatal hypoxia ischemia is a major cause of neurodevelopmental impairment in the newborn, associated with risk for motor, behavioral and cognitive impaired outcomes. We used an established mouse model of maternal hypoxia to examine the immediate molecular responses of signaling pathways associated with both cell death and neurogenesis. We also characterized responses to maternal pre-treatment with MgSO(4). Maternal hypoxia at embryonic day 17 (E17) failed to trigger inflammation or cell death in fetal brain at 24 h after hypoxia. However, maternal hypoxia decreased levels of neuronal migration signaling: Reelin (53% of control), Disabled 1 (Dab1, 77% of control), and amyloid precursor protein (APP, 64% of control) 2 h after the insult. These changes persisted for 24 h. At later times, Reelin levels in hippocampi of newborns in the maternal hypoxia-treated group increased compared to controls. Full protection from maternal hypoxia effects on hippocampal Reelin levels resulted from maternal pre-treatment with MgSO(4). Hypoxia and MgSO(4) increased radial and lateral migration distance in the CA1 four days after the insult, while in the DG the hypoxia treatment alone increased migration. Maternal hypoxia and MgSO(4) pre-treatment also stimulated hippocampal expression of genes related to neurogenesis, such as BDNF and NeuroD4. Taken together, the long-term neurodevelopmental outcome of prenatal and perinatal hypoxia may depend on perturbation of developmental signals that affect neuronal migration.

Fatal transplacental neosporosis in a deer (Cervus eldi siamensis).

Neospora caninum tissue cysts were found in sections of the brain from a full-term stillborn deer of Eld (Cervus eldi siamensis) from a zoo in France. There was N. caninum-associated nonsuppurative encephalitis and the diagnosis was confirmed in immunohistochemical staining with antibodies specific to N. caninum.