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The diverse inflammatory response after cerebral microbleeds includes coordinated microglial migration and proliferation
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May 29 2018
Source: Stroke. 49(7):1719-1726 -
Alternative Title:Stroke
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Personal Author:
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Description:Background and Purpose
Cerebral microbleeds are linked to cognitive decline, but it remains unclear how they impair neuronal function. Infarction is not typically observed near microbleeds, suggesting more subtle mechanisms, such as inflammation, may play a role. Due to their small size and largely asymptomatic nature, real-time detection and study of spontaneous cerebral microbleeds in humans and animal models is difficult.
Methods
We used in vivo two-photon microscopy through a chronic cranial window in adult mice to follow the inflammatory response after a cortical microhemorrhage of ∼100-μm diameter, induced by rupturing a targeted cortical arteriole with a laser.
Results
The inflammatory response included the invasion of blood borne leukocytes, the migration and proliferation of brain resident microglia, and the activation of astrocytes. Nearly all inflammatory cells responding to the microhemorrhage were brain-resident microglia, but a small number of CX3CR1+ and CCR2+ macrophages, ultimately originating from the invasion of blood-borne monocytes, were also found near the lesion. We found a coordinated pattern of microglia migration and proliferation, where microglia within 200 μm of the microhemorrhage migrated toward the lesion over hours to days. In contrast, microglia proliferation was not observed until ∼40 hours after the lesion and occurred primarily in a shell-shaped region where the migration of microglia decreased their local density. This data suggests that local microglia density changes may trigger proliferation. Astrocytes activated in a similar region as microglia, but delayed by a few days. By two weeks, this inflammatory response had largely resolved.
Conclusions
While microhemorrhages are small in size, the brain responds to a single bleed with an inflammatory response that involves brain-resident and blood-derived cells, persists for weeks, and may impact the adjacent brain microenvironment.
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Pubmed ID:29844029
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Pubmed Central ID:PMC6019563
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