TY - JOUR
T1 - A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules
AU - Shaked, Iftach
AU - Foo, Conrad
AU - Mächler, Philipp
AU - Liu, Rui
AU - Cui, Yingying
AU - Ji, Xiang
AU - Broggini, Thomas
AU - Kaminski, Tomasz
AU - Suryakant Jadhav, Suchita
AU - Sundd, Prithu
AU - Firer, Michael
AU - Devor, Anna
AU - Friedman, Beth
AU - Kleinfeld, David
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2024/2
Y1 - 2024/2
N2 - 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.
AB - 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.
KW - Imaging
KW - neutrophils
KW - platelets
KW - reactive oxygen species
KW - transient hyperglycemia
UR - http://www.scopus.com/inward/record.url?scp=85171865366&partnerID=8YFLogxK
U2 - 10.1177/0271678X231203023
DO - 10.1177/0271678X231203023
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AN - SCOPUS:85171865366
SN - 0271-678X
VL - 44
SP - 252
EP - 271
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 2
ER -