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

ABSTRACT: Intraventricular hemorrhage (IVH) remains a major neurological complication of prematurity that results in cerebral palsy, hydrocephalus, and cognitive deficits. No effective therapy exists to prevent these disorders in infants with IVH. IVH triggers inflammation, cellular infiltration and white matter injury following neurobehavioural deficits.

ORGANISM(S): Oryctolagus cuniculus

PROVIDER: GSE185438 | GEO | 2022/12/31

REPOSITORIES: GEO

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

Project description:Intraventricular hemorrhage (IVH) remains a major neurological complication of prematurity that results in cerebral palsy, hydrocephalus, and cognitive deficits. No effective therapy exists to prevent these disorders in infants with IVH. IVH triggers inflammation, cellular infiltration and white matter injury following neurobehavioural deficits.

2022-12-31 | GSE198497 | GEO

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.

2018-10-27 | GSE121867 | GEO

Discovering Haematoma-Stimulated Circuits for Secondary Brain Injury after Intraventricular Haemorrhage by Spatial Transcriptome Analysis

Project description:Intraventricular haemorrhage (IVH) is one of the common complications after various acute brain injuries, leading to severe mortality and mobility, with great burdens on economics and society. Recently, a CLEAR III trial (NCT00784134) employing alteplase effectively cleared intraventricular haematoma but did not demonstrate adequate neuro behavioural benefits for patients. Therefore, the present study sought to investigate the pathophysiology of how these haematoma stimulations in ventricles cause neurological dysfunction. An autologous blood stereotactic injection model was employed to establish and mimic secondary IVH in mice, followed by our innovated spatial transcriptome sequencing-based bioinformatic algorithm to investigate the 3D spatial brain regions affected by the primary stimulation of haematoma in the ipsilateral ventricle after IVH, as well as related cell-cell communication strength and pathway analysis. These data illustrate that the three main 3D global pseudospace-time trajectory bundles represent the main neural circuits from the lateral ventricle to the hippocampus and primary cortex induced by experimental intraventricular haematoma stimulation. Further analysis indicated a rapid response in the primary cortex, as well as a direct and integrated effect on the hippocampus after IVH. To the best of our knowledge, this is the first study to interrogate secondary brain injury after IVH by using spatial transcriptome sequencing and bioinformatics analysis. These data could provide more helpful information on the pathophysiological mechanism of IVH in patients after acute brain injury, as well as for the bioinformatics analysis strategies for similar studies in the future.

2022-11-19 | GSE214349 | GEO

PPARg activation enhances myelination and neurological recovery in premature rabbits with intraventricular hemorrhage

Project description:We hypothesized that activation of PPARg would enhance myelination, reduce hydrocephalus, and promote neurological recovery in newborns with IVH. These hypotheses were tested in preterm rabbit model of IVH; autopsy brain samples from premature infants with and without IVH were analyzed. We found that IVH augmented PPARg expression in microglia of both preterm human infants and rabbit kits. The treatment with PPARg agonist or PPARg overexpression by adenovirus delivery further elevated PPARg levels in microglia, reduced pro-inflammatory cytokines, increased microglial phagocytosis, and improved oligodendrocyte progenitor cell (OPC) maturation in kits with IVH. Transcriptomic analyses of OPCs identified previously unrecognized PPARg-induced novel genes for purinergic signaling, cAMP generation, and antioxidant production, which would reprogram these progenitors toward promoting myelination. RNA-seq analyses of microglia revealed PPARg-triggered downregulation of several pro-inflammatory genes and transcripts having roles in Parkinson’s disease and amyotrophic lateral sclerosis, contributing to neurological recovery in kits with IVH. Accordingly, PPARg activation enhanced myelination and neurological function in kits with IVH.

2021-08-27 | GSE182718 | GEO

Expression data of E16 GFAP-tTA: TetO-VEGF-A164 bitransgenic embryos compared to wild type

Project description:Overexpression of VEGF (vascular endothelial growth factor) in the germinal matrix of the brain causes GMH-IVH-like anomalies (Germinal matrix hemorrhage [GMH]; intraventricular hemorrhage [IVH]). This dataset provides the list of differentially expressed genes in the brain cortices of embryos with transgene directed overexpression of VEGF. Eight samples were analyzed, including four control and four with induced over expression of VEGF. A simple unpaired T-test was used for analysis, with GeneSpring software,

2013-06-14 | E-GEOD-47903 | biostudies-arrayexpress

Expression data of E16 GFAP-tTA: TetO-VEGF-A164 bitransgenic embryos compared to wild type

2013-06-14 | GSE47903 | GEO

Sonic hedgehog Activation Restores Interneurons and Cognitive Function in Newborns with Intraventricular Hemorrhage

Project description:We hypothesized that the occurrence of IVH would reduce interneuron neurogenesis in the medial ganglionic eminence and diminish the population of parvalbumin+ and somatostatin+ cortical interneurons. Since Sonic Hedgehog promotes the production of cortical interneurons, we also postulated that the activation of Sonic Hedgehog signaling might restore neurogenesis, cortical interneuron population, and neurobehavioral function in premature newborns with IVH.

2022-08-06 | GSE210477 | GEO

Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage

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.

2020-06-01 | GSE124361 | GEO

Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke

Project description:Oligodendrocyte progenitor cells (OPCs) differentiate to myelin-producing mature oligodendrocytes and enwrap growing or demyelinated axons during development and post central nervous diseases. Failure of remyelination due to cell death or undifferentiation of OPC contributes to severe neurologic deficits and motor dysfunction. However, how to prevent the cell death of OPCs is still poorly understood, especially in hemorrhagic diseases. In this current study, we injected autologous blood into the mouse lateral ventricular to study the hemorrhage induced OPC cell death in vivo. The integrity of the myelin sheath of the corpus callosum was disrupted post intraventricular hemorrhage (IVH) assessed by using magnetic resonance imaging, immunostaining, and transmission electron microscopy. Consistent with the severe demethylation, we observed massive cell death of oligodendrocyte lineages in the periventricular area. In addition, we found that ferroptosis is the major cell death form in Hemin-induced OPC death by using RNA-seq analysis, and the mechanism was glutathione peroxidase 4 (GPx4) expression and activity reduction-resulted lipid peroxide accumulation. Furthermore, inhibition of ferroptosis rescued OPC cell death in vitro, and in vivo attenuated IVH-induced white matter injury and promoted recovery of neurological function. These data demonstrate that ferroptosis is an essential form of OPC cell death in hemorrhagic stroke, and rescuing ferroptotic OPCs could serve as a therapeutic target for stroke and related diseases.

2022-02-24 | GSE197104 | GEO

Single-cell RNA sequencing (scRNAseq) data from Ventricular-Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) cells, and Scope-Seq data from Ventricular-Subventricular Zone (V-SVZ)

Project description:We performed large-scale single cell profiling of dissociated V-SVZ and OB cells from the same animal carrying either the hGFAP::CreERT2; Rosa26LSL-TdTomato (GCERT2) reporter, or ratNes::FLPOER; Rosa26FSF-TdTomato (NesFLPO) reporter. Scope-Seq profiling was performed on dissociated V-SVZ cells from C57BL/6J animals.

2020-06-21 | GSE134918 | GEO

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