Shaked Iftach, Foo Conrad, Mächler Philipp, Liu Rui, Cui Yingying, Ji Xiang, Broggini Thomas, Kaminski Tomasz, Suryakant Jadhav Suchita, Sundd Prithu, Firer Michael, Devor Anna, Friedman Beth, Kleinfeld David
Department of Physics, University of California at San Diego, La Jolla, CA, USA.
The Adelson Medical School, Ariel University, Ariel, Israel.
J Cereb Blood Flow Metab. 2024 Feb;44(2):252-271. doi: 10.1177/0271678X231203023. Epub 2023 Sep 22.
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 -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 -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.
在可控的生理条件下研究短暂性高血糖如何导致脑血管疾病一直是一项挑战。我们使用放大的超短激光脉冲在目标位置对脑微静脉内皮进行物理破坏。这种血管破坏是在向健康小鼠单次注射具有代谢活性的葡萄糖引发短暂性高血糖的情况下进行的。观察到的对激光诱导破坏的实时反应包括快速血清外渗、血小板聚集和中性粒细胞募集。血小板抑制剂、活性氧清除剂和一氧化氮供体可在药理学上改善血栓炎症。作为对照，注射代谢惰性葡萄糖的小鼠血管血栓炎症明显减轻。糖尿病小鼠的微静脉对激光诱导破坏表现出类似反应，恢复正常血糖可减轻损伤。我们的方法提供了一种可控方法，用于探究短暂性代谢和物理性血管扰动之间的协同作用，并可揭示脑病理生理学的新方面。
