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Diverse Inflammatory Response After Cerebral Microbleeds Includes Coordinated Microglial Migration and Proliferation.

TitleDiverse Inflammatory Response After Cerebral Microbleeds Includes Coordinated Microglial Migration and Proliferation.
Publication TypeJournal Article
Year of Publication2018
AuthorsAhn SJi, Anrather J, Nishimura N, Schaffer CB
JournalStroke
Date Published2018 May 29
ISSN1524-4628
Abstract

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. Because of their small size and largely asymptomatic nature, real-time detection and study of spontaneous cerebral microbleeds in humans and animal models are difficult.

METHODS: We used in vivo 2-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. These data suggest that local microglia density changes may trigger proliferation. Astrocytes activated in a similar region as microglia but delayed by a few days. By 2 weeks, this inflammatory response had largely resolved.

CONCLUSIONS: Although 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.

DOI10.1161/STROKEAHA.117.020461
Alternate JournalStroke
PubMed ID29844029
Grant ListR01 NS081179 / NS / NINDS NIH HHS / United States
R21 NS080098 / NS / NINDS NIH HHS / United States