Abstract
A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.
Highlights
Recent advances in neonatal care have significantly improved the survival rate of preterm infants, with low birth weight or with medical conditions
The Human amniotic fluid stem cells (hAFSCs) used in this study were evaluated for differentiation potential and surface markers to ensure that they met the definition of Mesenchymal stem cells (MSCs)
We previously reported a reduction in neuroinflammation in the entire hippocampus after hAFSC treatment, in this study, we analyzed neuroinflammation in three hippocampal regions, viz., CA1, CA3, and dentate gyrus (DG)
Summary
Recent advances in neonatal care have significantly improved the survival rate of preterm infants, with low birth weight or with medical conditions. The mortality rate of neonatal sepsis is very high, being 10–30% [1,2,3]. Neonatal sepsis survivors often suffer from severe functional disabilities for a long time. A systemic inflammatory response induces multiple organ dysfunction and can often cause hypoperfusion, hypoxia, and free radical damage to the brain, resulting in poor long-term neurological outcomes [5,6,7,8]. A number of treatments for neonatal sepsis have been evaluated. There is presently no effective therapy for the treatment or prevention of neonatal sepsis besides antibiotics and supportive care. It is important to develop innovative and efficacious strategies to reduce neonatal sepsis-related morbidity and mortality
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