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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:IntroductionCentral nervous system (CNS) diseases, such as neurodegenerative disorders and brain diseases caused by acute injuries, are important, yet challenging to study due to disease lesion locations and other complexities.MethodsUtilizing the powerful method of spatial transcriptome analysis together with novel algorithms we developed for the study, we report here for the first time a 3D trajectory map of gene expression changes in the brain following acute neural injury using a mouse model of intraventricular hemorrhage (IVH). IVH is a common and representative complication after various acute brain injuries with severe mortality and mobility implications.ResultsOur data identified three main 3D global pseudospace-time trajectory bundles that represent the main neural circuits from the lateral ventricle to the hippocampus and primary cortex affected by experimental IVH stimulation. Further analysis indicated a rapid response in the primary cortex, as well as a direct and integrated effect on the hippocampus after IVH stimulation.DiscussionThese results are informative for understanding the pathophysiological changes, including the spatial and temporal patterns of gene expression changes, in IVH patients after acute brain injury, strategizing more effective clinical management regimens, and developing novel bioinformatics strategies for the study of other CNS diseases. The algorithm strategies used in this study are searchable via a web service (www.combio-lezhang.online/3dstivh/home).

| S-EPMC9941151 | biostudies-literature

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

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

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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.

2022-11-17 | PXD038189 |

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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The characterisation of protein binding in paediatric extracorporeal membrane oxygenation (ECMO) circuits

Project description:The present study aims to characterise proteins bound to circuits collected from children on extracorporeal membrane oxygenation (ECMO). ECMO circuits were collected from 6 patients. Quantification of concentrations for proteins bound to the ECMO circuit samples was performed using bicinchoninic acid (BCA) protein assay, whilst characterisation of the bound proteome was performed using Data-independent acquisition Mass Spectrometry (DIA-MS). Reactome Over-representation Pathway Analyses tool was used to identify functional pathways corresponding to the common proteins bound to circuits across all patients.

2024-10-07 | PXD045889 | Pride

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

Discovering the Genetic Basis of Cleft Palate: CIDR

Project description:Discovering the Genetic Basis of Cleft Palate: CIDR

| PRJNA671434 | ENA

Discovering the Genetic Basis of Cleft Palate: CIDR

Project description:Discovering the Genetic Basis of Cleft Palate: CIDR

| PRJNA671433 | ENA