A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules

Iftach Shaked, Conrad Foo, Philipp Mächler, Rui Liu, Yingying Cui, Xiang Ji, Thomas Broggini, Tomasz Kaminski, Suchita Suryakant Jadhav, Prithu Sundd, Michael Firer, Anna Devor, Beth Friedman, David Kleinfeld

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled physiological conditions. We use amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium at targeted locations. This vessel disruption is performed in conjunction with transient hyperglycemia from a single injection of metabolically active D-glucose into healthy mice. The observed real-time responses to laser-induced disruption include rapid serum extravasation, platelet aggregation, and neutrophil recruitment. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, and by a nitric oxide donor. As a control, vessel thrombo-inflammation is significantly reduced in mice injected with metabolically inert L-glucose. Venules in mice with diabetes show a similar response to laser-induced disruption and damage is reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies between transient metabolic and physical vascular perturbations and can reveal new aspects of brain pathophysiology.

Original languageEnglish
Pages (from-to)252-271
Number of pages20
JournalJournal of Cerebral Blood Flow and Metabolism
Volume44
Issue number2
DOIs
StatePublished - Feb 2024

Keywords

  • Imaging
  • neutrophils
  • platelets
  • reactive oxygen species
  • transient hyperglycemia

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