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Diverse Inflammatory Response After Cerebral Microbleeds Includes Coordinated Microglial Migration and Proliferation
Sung Ji Ahn1, Josef Anrather2, Nozomi Nishimura1
1From the Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY (S.J.A., N.N., C.B.S.).
Stroke
|May 31, 2018
Summary
Cerebral microbleeds trigger an inflammatory response involving brain and blood cells. This response, including microglia migration and proliferation, resolves within weeks but may affect the brain microenvironment.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Cerebral microbleeds are associated with cognitive decline.
- Mechanisms linking microbleeds to neuronal dysfunction are not fully understood.
- Subtle mechanisms like inflammation are suspected due to lack of infarction near microbleeds.
Purpose of the Study:
- To investigate the inflammatory response to a single cortical microhemorrhage in vivo.
- To characterize the cellular players and temporal dynamics of the brain's reaction to microbleeds.
Main Methods:
- Induction of a cortical microhemorrhage (≈100 µm diameter) in adult mice using laser-induced arteriole rupture.
- Real-time monitoring of the inflammatory response using in vivo 2-photon microscopy through a chronic cranial window.
Main Results:
- Inflammatory response involved blood-borne leukocytes, brain-resident microglia, and astrocytes.
- Microglia exhibited coordinated migration towards the lesion followed by delayed proliferation.
- Blood-borne monocytes contributed a small population of macrophages (CX3CR1+, CCR2+).
- Astrocyte activation was observed, delayed by a few days relative to microglia.
- The inflammatory response largely resolved within two weeks.
Conclusions:
- Even small cerebral microbleeds elicit a significant inflammatory response.
- This response involves both resident and blood-derived immune cells.
- The inflammation persists for weeks and can impact the surrounding brain tissue.
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