Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted deletion of astrocytic Nhe1 stimulates Wnt/β-catenin-mediated BBB repair and angiogenesis after ischemic stroke

ABSTRACT: Targeted deletion of astrocytic Nhe1 stimulates Wnt/β-catenin-mediated BBB repair and angiogenesis after ischemic stroke

PROVIDER: PRJNA608486 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Targeted deletion of astrocytic Nhe1 stimulates Wnt/β-catenin-mediated BBB repair and angiogenesis after ischemic stroke

Project description:Roles of reactive perivascular astrocytes in dysregulation of the blood-brain barrier (BBB) function and cerebral perfusion are not well defined. Here, we investigated transformation of reactive astrocyte function for vascular repair after ischemic stroke by targeted deletion of astrocytic Na+/H+ exchanger isoform 1 in Gfap-CreERT2+/-;Nhe1f/f (Nhe1 Astro-KO) mice. Control Gfap-CreERT2+/-;Nhe1f/f (wild-type) mice displayed BBB damage (elevated endothelial transcytosis and intracellular vesicles) and persistent cerebral hypoperfusion in an ischemic stroke model (transient middle cerebral artery occlusion). In contrast, Nhe1 Astro-KO mice exhibited significantly less endothelial transcytosis and vesicle formation, and increased angiogenesis and cerebral blood perfusion (CBF) post-stroke. Bulk RNA-sequencing transcriptome analysis of isolated GFAP+ reactive astrocytes from wild-type and Nhe1 Astro-KO ischemic brains revealed that ~177 genes were differentially upregulated, with the Wnt7a mRNA among the top upregulated genes, along with additional Wnt pathway genes (Wnt7b, Fzd9, Fzd10, and Ndp). Abundant Wnt7a/b and β-catenin protein expression was detected in cerebral vessels of Nhe1 Astro-KO ischemic brains but not in the wild-type brains. Selective activation of Wnt/β-catenin pathway in cerebral vessels of Nhe1 Astro-KO ischemic brains was further validated using the Wnt reporter line TCF/LEF::H2B-eGFP; Gfap-CreERT2+/-;Nhe1f/f mice. Lastly, the role of Wnt/β-catenin pathway in resistance of Nhe1 Astro-KO mice to stroke-mediated BBB damage was tested by administration of Wnt/β-catenin inhibitor XAV-939. Taken together, we report that transforming reactive astrocyte function by upregulating astrocytic Wnt/β-catenin signaling activity is a novel mechanism to reduce the BBB endothelial damage, stimulate vascular repair, and restore cerebral blood flow after ischemic stroke.

2020-12-08 | GSE145839 | GEO

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.

2024-05-23 | GSE238125 | GEO

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

Zebrafish BBB transcriptome

Project description:Zebrafish BBB transcriptome

| PRJNA436028 | ENA

Indoxyl sulfate stimulates angiogenesis by regulating reactive oxygen species production via CYP1B1

Project description:Indoxyl sulfate stimulates angiogenesis by regulating reactive oxygen species production via CYP1B1

| PRJNA547986 | ENA

Selective knockout of astrocytic Na+ /H+ exchanger isoform 1 reduces astrogliosis, BBB damage, infarction, and improves neurological function after ischemic stroke.

Project description: Not available

| S-EPMC5705024 | biostudies-literature

Gene expression data of BBB and BCB two-cell embryos

Project description:We constructed one-cell stage embryos by maternal pronuclear (mPN) transfer having B6 ooplasm, B6 paternal PN (pPN), and either B6 or C3H mPN (BBB and BCB, respectively). We collected embryos of each type that were either treated (BBB+a, BCB+a) or untreated with Î±-amanitin (BBB, BCB) at the two-cell stage for microarray analysis. Comparison of the transcriptomes of these different kinds of embryos revealed genes for which expression differs according to maternal PN strain of origin, and the Î±-amanitin data revealed which of these differences is due to gene transcription, as opposed to any transcription-independent differences attributable to ooplasm-derived maternal mRNA pools. There are 4 replicates for each kind/treatment two-cell embryos (BBB, BCB, BBB+a, BCB+a).

2010-03-22 | E-GEOD-17886 | biostudies-arrayexpress

Transcriptome analysis after BBB-EC migration

Project description:A monolayer of hCMEC/D3 (BBB-EC) was grown in an insert. After reaching confluency, BBB-EC were treated with TNFa and IFNg for 24h. Next, BBB-EC were washed. Tregs were isolated from human blood (both healthy donors (HD)and untreated RRMS patients) and added to the upper chamber of the insert or were cultured in the BBB-EC medium as control (untouched_1). They were let to migrate for 24h and the upper fraction (non-migrated_2) and lower fraction (migrated_3) were collected.

2024-02-11 | GSE255171 | GEO

Synthetic VSMCs induce BBB disruption mediated by MYPT1 in ischemic stroke.

Project description: Not available

| S-EPMC8441154 | biostudies-literature