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Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate

ABSTRACT: Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate

PROVIDER: PRJNA926592 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23193423.fastq.gz	Fastqsanger.gz
	SRR23193424.fastq.gz	Fastqsanger.gz
	SRR23193425.fastq.gz	Fastqsanger.gz
	SRR23193426.fastq.gz	Fastqsanger.gz
	SRR23193427.fastq.gz	Fastqsanger.gz

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Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate

Project description:Derangements of the blood-brain barrier (BBB) or blood-retinal barrier (BRB) occur in disorders ranging from stroke, cancer, diabetic retinopathy, and Alzheimer's disease. The Norrin/FZD4/TSPAN12 pathway activates WNT/-catenin signaling, which is essential for BBB and BRB function. However, systemic pharmacologic FZD4 stimulation is hindered by obligate palmitoylation and insolubility of native WNTs and suboptimal properties of the FZD4-selective ligand Norrin. Here, we developed L6-F4-2, a non-lipidated, FZD4-specific surrogate with significantly improved sub-picomolar affinity versus native Norrin. In Norrin knockout (NdpKO) mice, L6-F4-2 not only potently reversed neonatal retinal angiogenesis deficits, but also restored BRB and BBB function. In adult C57Bl/6J mice, post-stroke systemic delivery of L6-F4-2 strongly reduced BBB permeability, infarction, and edema, while improving neurologic score and capillary pericyte coverage. Our findings reveal systemic efficacy of a bioengineered FZD4-selective WNT surrogate during ischemic BBB dysfunction, with general applicability to adult CNS disorders characterized by an aberrant blood-brain barrier.

2023-01-31 | GSE223498 | GEO

Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate (bulk)

2023-01-31 | GSE223628 | GEO

Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate (bulk)

Project description:Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate (bulk)

| PRJNA926996 | ENA

Gene expression analysis of peripheral whole blood RNA following ischemic stroke

Project description:The purpose of this project was to elucidate gene expression in the peripheral whole blood of acute ischemic stroke patients to identify a panel of genes for the diagnosis of acute ischemic stroke. Peripheral blood samples were collected in Paxgene Blood RNA tubes from stroke patients who were >18 years of age with MRI diagnosed ischemic stroke and controls who were non-stroke neurologically healthy. The results suggest a panel of genes can be used to diagnose ischemic stroke, and provide information about the biological pathways involved in the response to acute ischemic stroke in humans. Total RNA extracted from whole blood in n=39 ischemic stroke patients compared to n=24 healthy control subjects.

2010-06-08 | E-GEOD-16561 | biostudies-arrayexpress

Epigenome analysis of ischemic stroke patients

Project description:We performed a genome-wide methylation study in whole-blood DNA from 404 ischemic stroke patient cohort, distributed across 3 ischemic stroke subtypes: Large-artery atherosclerosis (n=132), Small-artery disease (n=141) and Cardio embolic (n=127) . Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites. We performed a genome-wide methylation study in whole-blood DNA from 185 ischemic stroke patient cohort. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites.

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Dynamic microglial gene expression profiles after ischemic stroke

Project description:Analysis of microglial gene expression profiles after ischemic stroke. Stroke is a complicated disease caused by the interaction of multiple celltypes. Results provide new insights into the molecular mechanisms underlying microglial activation after ischemic stroke.

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Dynamic astrocytic gene expression profiles after ischemic stroke

Project description:Analysis of astrocytic gene expression profiles after ischemic stroke. Stroke is a complicated disease caused by the interaction of multiple celltypes. Results provide new insights into the molecular mechanisms underlying astrocytic activation after ischemic stroke.

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Gene expression analysis of peripheral whole blood RNA following ischemic stroke

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Ischemic Stroke Genetics Study (ISGS)

Project description:Ischemic Stroke Genetics Study (ISGS)

| PRJNA75377 | ENA

Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke

Project description:Intermittent fasting is previously reported to exhibit neuroprotection against experimental ischemic stroke. However, the detailed understanding of protection mechanisms are lacking. By observing the overall transcriptomic changes in each timepoint of ischemic stroke would benefit the understanding of underlying active pathways and mechanisms. Here, we conduct experimental MCAO ischemic stroke on mice exposed to different daily intermittent fasting method to compare not only among the ischemic stroke timepoints but also the efficacy of different intermittent fasting interventions. Our current study presented the transcriptomic changes for the first time in specific timepoints of ischemic stroke as well as under the condition of intermittent fasting. A number of neuroprotective mechanisms-related genes were significantly affected by intermittent fasting conditions in differential manners.

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