Endothelial glycocalyx dysfunction in the setting of mechanical thrombectomy: a conceptual link between cardiometabolic vulnerability and microvascular reperfusion failure
- 1Clinical Medical College, Qinghai University
- 2Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences
Abstract
Mechanical thrombectomy (MT) has made macrovessel reopening achievable in acute ischemic stroke, but angiographic success does not ensure effective tissue-level reperfusion or microvascular oxygen delivery. This narrative review examines endothelial glycocalyx dysfunction as a plausible blood-facing interface that may connect pre-existing cardiometabolic vulnerability with post-thrombectomy microvascular dysfunction. Targeted English-language literature from PubMed/MEDLINE, Web of Science, Embase, and Google Scholar through 30 April 2026 was synthesized, with emphasis on MT, impaired microvascular reperfusion (IMR), no-reflow, blood–brain barrier (BBB) and neurovascular-unit (NVU) biology, glycocalyx-related biomarkers, cardiometabolic risk, perfusion imaging, and microcirculatory rescue. The evidence base is heterogeneous and is explicitly separated into direct human MT/LVO evidence, indirect human biomarker or imaging evidence, experimental cerebral evidence, non-cerebral/cross-disease vascular evidence, and hypothesis-generating mechanistic inference. Ischemic priming, abrupt reperfusion, oxidative and inflammatory stress, complement activation, metabolic stress, distal embolization, device-endothelial trauma, and host vulnerability may converge on the luminal endothelial surface. Glycocalyx dysfunction may amplify leukocyte adhesion and capillary plugging, platelet adhesion and microthrombosis, impaired mechanosensing and nitric-oxide signaling, BBB destabilization, and heterogeneous capillary flow; however, direct causal proof in human MT is lacking. Circulating syndecan-1, heparan sulfate, and hyaluronan are therefore best interpreted as time- and compartment-dependent systemic signals rather than direct readouts of the cerebral glycocalyx. Post-EVT microcirculatory rescue trials show that downstream perfusion may remain therapeutically actionable, but they do not demonstrate glycocalyx repair as the operative mechanism. A practical translational strategy is to combine serial, compartment-annotated biomarkers with prespecified early perfusion/barrier imaging and tissue endpoints, while explicitly modeling cardiometabolic vulnerability and competing microvascular mechanisms. The glycocalyx framework should therefore be considered a testable network hypothesis rather than an established primary cause of post-thrombectomy no-reflow or futile recanalization.
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BibTeX
@article{wu2026endothelial,
title = {{Endothelial glycocalyx dysfunction in the setting of mechanical thrombectomy: a conceptual link between cardiometabolic vulnerability and microvascular reperfusion failure}},
author = {Xusheng Wu and Sufu Mi and Jing Ma and Yue Xing and Guangbin Li and Zongyu Cao and Xingjiang Xiong},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1919445},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1919445/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Endothelial glycocalyx dysfunction in the setting of mechanical thrombectomy: a conceptual link between cardiometabolic vulnerability and microvascular reperfusion failure
AU - Xusheng Wu
AU - Sufu Mi
AU - Jing Ma
AU - Yue Xing
AU - Guangbin Li
AU - Zongyu Cao
AU - Xingjiang Xiong
PY - 2026
DA - 2026/10/21
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1919445
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1919445/full
AB - Mechanical thrombectomy (MT) has made macrovessel reopening achievable in acute ischemic stroke, but angiographic success does not ensure effective tissue-level reperfusion or microvascular oxygen delivery. This narrative review examines endothelial glycocalyx dysfunction as a plausible blood-facing interface that may connect pre-existing cardiometabolic vulnerability with post-thrombectomy microvascular dysfunction. Targeted English-language literature from PubMed/MEDLINE, Web of Science, Embase, and Google Scholar through 30 April 2026 was synthesized, with emphasis on MT, impaired microvascular reperfusion (IMR), no-reflow, blood–brain barrier (BBB) and neurovascular-unit (NVU) biology, glycocalyx-related biomarkers, cardiometabolic risk, perfusion imaging, and microcirculatory rescue. The evidence base is heterogeneous and is explicitly separated into direct human MT/LVO evidence, indirect human biomarker or imaging evidence, experimental cerebral evidence, non-cerebral/cross-disease vascular evidence, and hypothesis-generating mechanistic inference. Ischemic priming, abrupt reperfusion, oxidative and inflammatory stress, complement activation, metabolic stress, distal embolization, device-endothelial trauma, and host vulnerability may converge on the luminal endothelial surface. Glycocalyx dysfunction may amplify leukocyte adhesion and capillary plugging, platelet adhesion and microthrombosis, impaired mechanosensing and nitric-oxide signaling, BBB destabilization, and heterogeneous capillary flow; however, direct causal proof in human MT is lacking. Circulating syndecan-1, heparan sulfate, and hyaluronan are therefore best interpreted as time- and compartment-dependent systemic signals rather than direct readouts of the cerebral glycocalyx. Post-EVT microcirculatory rescue trials show that downstream perfusion may remain therapeutically actionable, but they do not demonstrate glycocalyx repair as the operative mechanism. A practical translational strategy is to combine serial, compartment-annotated biomarkers with prespecified early perfusion/barrier imaging and tissue endpoints, while explicitly modeling cardiometabolic vulnerability and competing microvascular mechanisms. The glycocalyx framework should therefore be considered a testable network hypothesis rather than an established primary cause of post-thrombectomy no-reflow or futile recanalization.
SN - 1664-2295
ER -