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RNA sequencing reveals novel macrophage transcriptome favoring neurovascular plasticity after ischemic stroke
- Source :
- J Cereb Blood Flow Metab
- Publication Year :
- 2019
- Publisher :
- SAGE Publications, 2019.
-
Abstract
- Blood monocytes/macrophages infiltrate the brain after ischemic stroke and critically influence brain injury and regeneration. We investigated stroke-induced transcriptomic changes of monocytes/macrophages by RNA sequencing profiling, using a mouse model of permanent focal cerebral ischemia. Compared to non-ischemic conditions, brain ischemia induced only moderate genomic changes in blood monocytes, but triggered robust genomic reprogramming in monocytes/macrophages invading the brain. Surprisingly, functional enrichment analysis of the transcriptome of brain macrophages revealed significant overrepresentation of biological processes linked to neurovascular remodeling, such as angiogenesis and axonal regeneration, as early as five days after stroke, suggesting a previously underappreciated role for macrophages in initiating post-stroke brain repair. Upstream Regulator analysis predicted peroxisome proliferator-activated receptor gamma (PPARγ) as a master regulator driving the transcriptional reprogramming in post-stroke brain macrophages. Importantly, myeloid cell-specific PPARγ knockout (mKO) mice demonstrated lower post-stroke angiogenesis and neurogenesis than wild-type mice, which correlated significantly with the exacerbation of post-stroke neurological deficits in mKO mice. Collectively, our findings reveal a novel repair-enhancing transcriptome in brain macrophages during post-stroke neurovascular remodeling. As a master switch controlling genomic reprogramming, PPARγ is a rational therapeutic target for promoting and maintaining beneficial macrophage functions, facilitating neurorestoration, and improving long-term functional recovery after ischemic stroke.
- Subjects :
- Angiogenesis
Neurogenesis
Neovascularization, Physiologic
Biology
Monocytes
Transcriptome
03 medical and health sciences
0302 clinical medicine
Cell Movement
Animals
Macrophage
cardiovascular diseases
Ischemic Stroke
030304 developmental biology
Mice, Knockout
0303 health sciences
Neuronal Plasticity
Sequence Analysis, RNA
Macrophages
Regeneration (biology)
Brain
RNA
Original Articles
Neurovascular bundle
Cell biology
Mice, Inbred C57BL
PPAR gamma
Neurology
Cerebrovascular Circulation
Ischemic stroke
Neurology (clinical)
Cardiology and Cardiovascular Medicine
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15597016 and 0271678X
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Accession number :
- edsair.doi.dedup.....713648265a0b040c63c14fdbda66aadc