Longitudinal intravital imaging of cerebral microinfarction reveals a dynamic astrocyte reaction leading to glial scar formation

• Published in: Glia Vol. 70; no. 5; pp. 975 - 988
• Main Authors: Lee, Jingu, Kim, Joon‐Goon, Hong, Sujung, Kim, Young Seo, Ahn, Soyeon, Kim, Ryul, Chun, Heejung, Park, Ki Duk, Jeong, Yong, Kim, Dong‐Eog, Lee, C. Justin, Ku, Taeyun, Kim, Pilhan
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2022; Wiley Subscription Services, Inc
• Subjects: Animals; Astrocytes; Astrocytes - metabolism; Blood vessels; Blood-brain barrier; Cerebral cortex; cerebral microinfarct; Collagen; Dementia disorders; Dextran; Dextrans; Dextrans - metabolism; Edema; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; glial scar formation; Gliosis - diagnostic imaging; Gliosis - etiology; Gliosis - metabolism; Imaging; Infarction - metabolism; Integrity; intravital imaging; Intravital Microscopy; Mice; Microvasculature; Neuroimaging; reactive astrocyte; blood-brain barrier; reactive astrocyte; intravital imaging; glial scar formation; cerebral microinfarct
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.24151

Cerebral microinfarct increases the risk of dementia. But how microscopic cerebrovascular disruption affects the brain tissue in cellular‐level are mostly unknown. Herein, with a longitudinal intravital imaging, we serially visualized in vivo dynamic cellular‐level changes in astrocyte, pericyte and neuron as well as microvascular integrity after the induction of cerebral microinfarction for 1 month in mice. At day 2–3, it revealed a localized edema with acute astrocyte loss, neuronal death, impaired pericyte‐vessel coverage and extravascular leakage of 3 kDa dextran (but not 2 MDa dextran) indicating microinfarction‐related blood–brain barrier (BBB) dysfunction for small molecules. At day 5, the local edema disappeared with the partial restoration of microcirculation and recovery of pericyte‐vessel coverage and BBB integrity. But brain tissue continued to shrink with persisted loss of astrocyte and neuron in microinfarct until 30 days, resulting in a collagen‐rich fibrous scar surrounding the microinfarct. Notably, reactive astrocytes expressing glial fibrillary acidic protein (GFAP) appeared at the peri‐infarct area early at day 2 and thereafter accumulated in the peri‐infarct until 30 days, inducing glial scar formation in cerebral cortex. Our longitudinal intravital imaging of serial microscopic neurovascular pathophysiology in cerebral microinfarction newly revealed that astrocytes are critically susceptible to the acute microinfarction and their reactive response leads to the fibrous glial scar formation. Main Points Long‐term intravital imaging revealed a fibrous collagen‐rich scar formation in the microinfarct with accumulation of GFAP+ reactive astrocytes, transient BBB dysfunction with impaired pericyte‐vessel coverage and neuronal loss.