Imaging a concussion and the ensuing immune response at the blood-brain barrier

• 成果类型: Article
• 署名作者: Nguyen, Rita H.; Newton, Michelle; Kratofil, Rachel M.; Scott, Brittney N. V.; Castanheira, Fernanda; Kim, Jung- seok; Ginhoux, Florent; Jung, Steffen; Kubes, Paul
• 署名单位: University of Calgary; Weizmann Institute of Science; Chinese Academy of Sciences; Shanghai Jiao Tong University; Agency for Science Technology & Research (A*STAR); A*STAR - Singapore Immunology Network (SIgN); UNICANCER; Gustave Roussy
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14059
• DOI: 10.1073/pnas.2414316122
• 发表日期: 2025-05-19
• 关键词: injury; microglia; DYNAMICS; receptor; models; cd36

摘要

Concussions can cause debilitating symptoms despite no evidence of structural changes on diagnostic imaging. The cellular events occurring in the brain parenchyma following concussion, especially repetitive concussion, are not well elucidated. We developed a concussion model to induce a confined area of injury without causing frank hemorrhage. Using intravital microscopy, we observe activation of the vasculature that supported neutrophil rolling and platelet adhesion but no overt cellular recruitment from blood into brain parenchyma. Activated resident, not monocyte-derived, macrophages relocated to the injury site via Cx3cr1 and phagocytosed dysfunctional/ detached astrocytes via scavenger receptors and TLR4, particularly after repetitive concussion. Additionally, microglia sealed areas of blood-brain barrier (BBB) disruption via purinergic pathways. Using a splitCre approach to dissect microglia and perivascular macrophages, we show that microglial invasion into the injury site is key to reducing BBB disruption. Our data suggest that microglia repair the BBB following concussion, but in doing so significantly alter the cellular ultrastructure of the brain milieu.