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Germinalmatrix-Intraventricular Hemorrhage induced Early Gene Expression Profile in Subventricular zone (SVZ) of developing rabbit forebrain

ABSTRACT: Germinalmatrix-Intraventricular Hemorrhage induced Early Gene Expression Profile in Subventricular zone (SVZ) of developing rabbit forebrain

PROVIDER: PRJNA769099 | ENA |

REPOSITORIES: ENA

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Germinalmatrix-Intraventricular Hemorrhage induced Early Gene Expression Profile in Subventricular zone (SVZ) of developing rabbit forebrain

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RNA Sequencing of CSF Samples from Patients with Intraventricular Hemorrhage and Neural Tube Defects

Project description:Intraventricular hemorrhage (IVH) is a significant complication of premature infants. With improved preterm infant survival, there is increased incidence of severe IVH, and the potential for lifelong neurodevelopmental deficits. Neurological complications are high in babies that develop hydrocephalus as a result of IVH and require a permanent ventriculoperitoneal (VP) shunt. Spina bifida is a congenital disorder caused by the incomplete closure of the neural tube. Hydrocephalus is also a common complication of spina bifida, presenting in 15 to 25% of cases. Often, when spina bifida is identified and surgically repaired, CSF shunting mechanisms are placed in a high percentage of cases. A better understanding of the events leading to the development of hydrocephalus will help clinicians make more informed decisions about the need for CSF shunting and other interventions. Extracellular RNAs (exRNAs) may be indicators of the multiple pathological events surrounding the development of hydrocephalus in subjects with intraventricular hemorrhage or spina bifida. exRNAs may also be indicators for the presence and magnitude of neurodevelopmental outcomes. Under that premise, we sequenced the total exRNA in CSF from children that had IVH or spina bifida, some of which developed hydrocephalus and/or had reported developmental delays.

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Project description:Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.

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subventricular zone progenitors healthy vs. Experimental Autoimmune Encephalomyelitis mice

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