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

Jingu Lee, Joon Goon Kim, Sujung Hong, Young Seo Kim, Soyeon Ahn, Ryul Kim, Heejung Chun, Ki Duk Park, Yong Jeong, Dong Eog Kim, C. Justin Lee, Taeyun Ku, Pilhan Kim

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)975-988
Number of pages14
JournalGlia
Volume70
Issue number5
DOIs
Publication statusPublished - 2022 May

Bibliographical note

Funding Information:
We would like to thank Dr. W. Chung (Korea Advanced Institute of Science and Technology, Korea) for providing the Aldh1l1‐GFP mouse, and Dr. Tomura and Dr. Miwa (Kyoto University, Japan) for providing the Kaede mouse. This work was supported by the Brain Research Program (2016M3C7A1913844) and the Basic Research Program (2020R1A2C3005694) funded by the Ministry of Science and ICT, Republic of Korea.

Funding Information:
We would like to thank Dr. W. Chung (Korea Advanced Institute of Science and Technology, Korea) for providing the Aldh1l1-GFP mouse, and Dr. Tomura and Dr. Miwa (Kyoto University, Japan) for providing the Kaede mouse. This work was supported by the Brain Research Program (2016M3C7A1913844) and the Basic Research Program (2020R1A2C3005694) funded by the Ministry of Science and ICT, Republic of Korea. Dr. D.-E. Kim was supported by the National Priority Research Center program (NRF-2021R1A6A1A03038865) and the Basic Science Research Program (NRF-2020R1A2C3008295) of the National Research Foundation of Korea. [Correction added on February 11, 2022, after first online publication: Acknowledgment section has been updated]

Funding Information:
National Research Foundation of Korea, Grant/Award Numbers: 2020R1A2C3005694, 2016M3C7A1913844 Funding information

Publisher Copyright:
© 2022 Wiley Periodicals LLC.

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

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