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

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

PROVIDER: PRJNA885047 | ENA |

REPOSITORIES: ENA

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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

Discovering hematoma-stimulated circuits for secondary brain injury after intraventricular hemorrhage by spatial transcriptome analysis.

Project description: Not available

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Discovering sORF-encoded Peptides Associated with Secondary Metabolism in Streptomyces

Project description:To investigate the effect of small peptides up to 100aa on the regulation of secondary metabolite synthesis during the fermentation of this strain S187. Differential expression of peptides within 100aa at different growth time points of strain S187.

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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 | GSE185438 | GEO

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

2022-12-31 | GSE198497 | GEO

Developmental Stage-Dependent Transcriptomic Responses to Neonatal Intraventricular Hemorrhage

Project description:Developmental Stage-Dependent Transcriptomic Responses to Neonatal Intraventricular Hemorrhage

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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.

2018-10-27 | GSE121867 | GEO

Developmental Stage-Dependent Transcriptomic Responses to Neonatal Intraventricular Hemorrhage

Project description:Neonatal intraventricular hemorrhage (IVH) is a major complication of preterm birth, yet how developmental stage influences the brain’s response to injury remains unclear. We performed single-nucleus RNA sequencing on rat brains 24 hours after IVH at postnatal day 2 (PND2) or day 5 (PND5) to define transcriptional responses across cell types. We identified 42 distinct cell populations and found that PND5 brains exhibited a markedly stronger immune and inflammatory response to IVH, with a threefold increase in differentially expressed genes compared to PND2. Microglia were the most perturbed cell type at both stages, showing increased oxidative stress and polarization toward both pro- and anti-inflammatory phenotypes at PND5. Ligand-receptor and regulon analysis revealed a shift from reparative IGF2 and TGF-β signaling at PND2 to proinflammatory Wnt signaling and activation of Runx1 and Stat5 at PND5. These findings highlight the importance of developmental timing in shaping the neuroimmune response to IVH and identify potential stage-specific therapeutic targets.

2026-02-11 | GSE302024 | 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

Cell Type-Specific Hormonal Signaling Configures Hypothalamic Circuits for Parenting

Project description:Parenting behavior emerges from hormonally sensitive circuits, but how distinct circuit components are affected by, and contribute to, sex and state dependent changes in infant caregiving remains unclear. Using cell type-specific approaches, we characterized two circuit nodes that are differentially configured by hormones to modulate infant-evoked behavior. An excitatory neuronal population in the anteroventral periventricular nucleus is only active in lactating mothers, increases virgin female caregiving when artificially stimulated and confers oxytocin sensitivity in mothers through a prolactin--STAT5b pathway. These neurons function upstream of another preoptic area population involved in male and female parenting, thus boosting caregiving by mothers. By contrast, androgen signaling in the latter preoptic population reshapes their intrinsic properties to promote pup-directed aggression, revealing cell type-specific tuning of social behavior circuits.

2026-01-12 | GSE316130 | GEO

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