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| Status |
Public on Feb 10, 2021 |
| Title |
Temporally Distinct Myeloid Cell Reponses Mediate Damage and Repair After Cerebrovascular Injury. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cerebrovascular injuries can cause severe edema and inflammation that adversely affect human health. Here, we observed recanalization after successful endovascular thrombectomy for acute large vessel occlusion was associated with cerebral edema and poor clinical outcomes in patients who experienced hemorrhagic transformation. To understand this process, we developed a cerebrovascular injury model using transcranial ultrasound that enabled spatiotemporal evaluation of resident and peripheral myeloid cells. We discovered that injurious and reparative responses diverged based on time and cellular origin. Resident microglia initially stabilized damaged vessels in a purinergic receptor-dependent manner, which was followed by influx of myelomonocytic cells that caused severe edema. Prolonged blockade of myeloid cell recruitment with anti-adhesion molecule therapy prevented severe edema but also promoted neuronal destruction and fibrosis by interfering with vascular repair later orchestrated by pro-inflammatory monocytes and pro-angiogenic repair-associated microglia (RAM). These data demonstrate how temporally distinct myeloid cell responses can contain, exacerbate, and ultimately repair a cerebrovascular injury.
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| Overall design |
Bulk RNA-Seq profiling of twelve different B6 mice (4 uninjured, 4 injured, 4 injured with αLFA1/VLA4).
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| Contributor(s) |
Mastorakos P, Mihelson N, Luby M, Burks SR, Johnson KR, Hsia AW, Witko J, Frank JA, Latour L, McGavern DB |
| Citation(s) |
33462481 |
| Submission date |
Nov 13, 2020 |
| Last update date |
Feb 10, 2021 |
| Contact name |
Kory R Johnson |
| E-mail(s) |
johnsonko@ninds.nih.gov
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| Phone |
301-402-1956
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| Organization name |
NINDS/NIH
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| Department |
DIR IT & Bioinformatics
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| Lab |
Bioinformatics Section
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| Street address |
10/3B01, 9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA678288 |
| SRA |
SRP292496 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE161424_RAW.tar |
16.0 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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