Work

Endothelial glycocalyx dysfunction in the setting of mechanical thrombectomy: a conceptual link between cardiometabolic vulnerability and microvascular reperfusion failure

Year: 2026

Type: review

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.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2026.1919445