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Published on: April 21, 2017
Endothelial injury in childhood stroke with cerebral arteriopathy: a cross-sectional study
Despina Eleftheriou1, Vijeya Ganesan, Ying Hong
1Paediatric Rheumatology Department, Institute of Child Health and Great Ormond St Hospital for Children, London, UK. d.eleftheriou@ich.ucl.ac.uk
Insights
Children with recurrent arterial ischemic stroke (AIS) show higher levels of circulating endothelial cells (CECs) and microparticles (MPs), indicating increased endothelial injury and thrombotic tendency compared to single AIS events.
Area of Science:
- Pediatric Neurology
- Vascular Biology
- Hematology
Background:
- Circulating endothelial cells (CECs) and microparticles (MPs) are biomarkers of endothelial injury and activation.
- These markers may play a role in the pathophysiology of arterial ischemic stroke (AIS).
Purpose of the Study:
- To investigate differences in CECs and MPs between children with single versus recurrent AIS events.
- To assess the functional significance of MPs in relation to AIS recurrence.
Main Methods:
- A cross-sectional study involving 46 children with AIS and cerebral arteriopathy.
- CECs and MPs were quantified using immunomagnetic bead extraction and flow cytometry.
- MP-mediated thrombin generation was assessed using a fluorogenic assay.
Main Results:
- Children with recurrent AIS exhibited significantly elevated levels of CECs compared to single AIS events and controls.
- Total circulating annexin V+ MPs, particularly those of endothelial or platelet origin expressing tissue factor, were higher in recurrent AIS cases.
- Enhanced MP-mediated thrombin generation was observed in children with recurrent AIS, linking inflammation, endothelial injury, and thrombotic tendency.
Conclusions:
- Indices of endothelial injury and cellular activation differ between single and recurrent childhood AIS events.
- This study highlights a potential role for CECs and MPs in understanding AIS pathophysiology and prognosis.
- The findings suggest these biomarkers may aid in risk stratification for recurrent AIS.
Objective:
Circulating endothelial cells (CECs) and microparticles (MPs) have been reported to reflect endothelial injury, cellular activation, and MP-mediated thrombin generation. We tested the hypothesis that these indices differ between children with cerebral arteriopathy and arterial ischemic stroke (AIS) recurrence, and those with a single event.
Methods:
This was a single-center cross-sectional study of 46 children with AIS and cerebral arteriopathy matched with pediatric controls. AIS recurrence was defined as new acute neurologic deficit with radiologic evidence of further cerebral infarction. CECs and MPs were identified with immunomagnetic bead extraction and flow cytometry, respectively. MP function as assessed by thrombin generation was determined using a fluorogenic assay.
Results:
Ten children had AIS recurrence while 36 had a single AIS event. CECs were raised in children with recurrent AIS, compared to those with no recurrence (p = 0.0001), and in controls (p = 0.0001). Total circulating annexin V+ MPs were significantly greater in children with recurrence than in those with no recurrence (p = 0.0020). These MPs were of endothelial or platelet origin, and a subpopulation expressed tissue factor. Finally, MP-mediated thrombin generation was enhanced in children with recurrent AIS compared to those with no recurrence (p = 0.0001), providing a link between inflammation, endothelial injury, and increased thrombotic tendency.
Conclusion:
Despite the wide spectrum of clinical and radiologic presentation of childhood AIS, indices of endothelial injury and cellular activation are different in patients with single and recurrent events. This novel approach has potential for furthering understanding of AIS pathophysiology and prognosis.
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