Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion

Desilles, Jean‐Philippe; Syvannarath, Varouna; Meglio, Lucas Di; Ducroux, Célina; Boisseau, William; Louedec, Liliane; Jandrot‐Perrus, Martine; Michel, Jean‐Baptiste; Mazighi, Mikaël; Ho‐Tin‐Noé, Benoît

doi:10.1161/jaha.117.007804

Cited by 59 publications

(62 citation statements)

References 11 publications

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“…Briefly, median patient age was 76 years (IQR = 69-83 years), and sex was similarly distributed (40% men, 60% women). The most Symptomatic intracranial hemorrhage, n (%) 6 (15) In-house mortality, n (%) 5 (13) Values are presented as number (percentage) for categorical variables and median (IQR) for continuous variables. prevalent comorbid disease was atrial fibrillation (50%), followed by hypertension (40%).…”

Section: Resultsmentioning

confidence: 99%

“…Experimental data suggest that immune cells and platelets contribute to the evolution of cerebral infarction . However, studies in humans are sparse, and data on immune cell accumulation and modulation during the hyperacute stage of ischemic stroke are lacking .…”

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confidence: 99%

“…10 Experimental data suggest that immune cells and platelets contribute to the evolution of cerebral infarction. [11][12][13][14][15] However, studies in humans are sparse, and data on immune cell accumulation and modulation during the hyperacute stage of ischemic stroke are lacking. 16,17 Animal studies indicate that even after brief episodes of cerebral ischemia, microvascular function is compromised, leading to focal no-reflow despite return of blood flow in the main vascular trunks.…”

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confidence: 99%

“…16,17 Animal studies indicate that even after brief episodes of cerebral ischemia, microvascular function is compromised, leading to focal no-reflow despite return of blood flow in the main vascular trunks. 18,19 Histological studies in these animals show very early accumulation of leukocytes and platelets in the microvasculature, 15,19,20 and there is increasing evidence that they functionally contribute to ischemic brain damage. [21][22][23] To overcome the translational road block with high failure rates in clinical studies of experimentally successful treatments, it is essential to get direct insights into pathophysiological processes in acute stroke patients.…”

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confidence: 99%

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Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke

Kollikowski

Schuhmann

Nieswandt

et al. 2020

Annals of Neurology

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Objective Bridging the gap between experimental stroke and patients by ischemic blood probing during the hyperacute stage of vascular occlusion is crucial to assess the role of inflammation in human stroke and for the development of adjunct treatments beyond recanalization. Methods We prospectively observed 151 consecutive ischemic stroke patients with embolic large vessel occlusion of the anterior circulation who underwent mechanical thrombectomy. In all these patients, we attempted microcatheter aspiration of 3 different arterial blood samples: (1) within the core of the occluded vascular compartment and controlled by (2) carotid and (3) femoral samples obtained under physiological flow conditions. Subsequent laboratory analyses comprised leukocyte counting and differentiation, platelet counting, and the quantification of 13 proinflammatory human chemokines/cytokines. Results Forty patients meeting all clinical, imaging, interventional, and laboratory inclusion criteria could be analyzed, showing that the total number of leukocytes significantly increased under the occlusion condition. This increase was predominantly driven by neutrophils. Significant increases were also apparent for lymphocytes and monocytes, accompanied by locally elevated plasma levels of the T‐cell chemoattractant CXCL‐11. Finally, we found evidence that short‐term clinical outcome (National Institute of Health Stroke Scale at 72 hours) was negatively associated with neutrophil accumulation. Interpretation We provide the first direct human evidence that neutrophils, lymphocytes, and monocytes, accompanied by specific chemokine upregulation, accumulate in the ischemic vasculature during hyperacute stroke and may affect outcome. These findings strongly support experimental evidence that immune cells contribute to acute ischemic brain damage and indicate that ischemic inflammation initiates already during vascular occlusion. Ann Neurol 2020;87:466–479

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke

Kollikowski

Schuhmann

Nieswandt

et al. 2020

Annals of Neurology

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“…New insights show that already very early during ischemia, neutrophils, and platelets are recruited to the ischemic brain and contribute to microvascular dysfunction (66,67). Otxoade-Amezaga and colleagues recently visualized an early influx of neutrophils to the brain after stroke, predominantly located within the intravascular space already early after reperfusion (68).…”

Section: Vwf-glycoprotein Ib Mediated Thromboinflammation In Ischemicmentioning

confidence: 99%

von Willebrand Factor and Platelet Glycoprotein Ib: A Thromboinflammatory Axis in Stroke

2019

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von Willebrand factor (VWF) and platelets are key mediators of normal hemostasis. At sites of vascular injury, VWF recruits platelets via binding to the platelet receptor glycoprotein Ibα (GPIbα). Over the past decades, it has become clear that many hemostatic factors, including VWF and platelets, are also involved in inflammatory processes, forming intriguing links between hemostasis, thrombosis, and inflammation. The so-called "thrombo-inflammatory" nature of the VWF-platelet axis becomes increasingly recognized in different cardiovascular pathologies, making it a potential therapeutic target to interfere with both thrombosis and inflammation. In this review, we discuss the current evidence for the thrombo-inflammatory activity of VWF with a focus on the VWF-GPIbα axis and discuss its implications in the setting of ischemic stroke.

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Thrombectomy with or without Intravenous Thrombolytics in Basilar Artery Occlusion

Maïer

Finitsis

Mazighi

et al. 2023

Annals of Neurology

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ObjectiveTwo randomized trials demonstrated the benefit of endovascular therapy (EVT) in patients suffering from a stroke due to a basilar artery occlusion (BAO). However, intravenous thrombolytic (IVT) use before EVT was low in these trials, questioning the added value of this treatment in this setting. We sought to investigate the efficacy and safety of EVT alone compared to IVT + EVT in stroke patients with a BAO.MethodsWe analyzed data from the Endovascular Treatment in Ischemic Stroke registry, a prospective, observational, multicenter study of acute ischemic stroke patients treated with EVT in 21 centers in France between 1 January 2015 and 31 December 2021. We included patients with BAO and/or intracranial vertebral artery occlusion and compared patients treated with EVT alone versus IVT + EVT after propensity score (PS) matching. Variables selected for the PS were pre‐stroke mRS, dyslipidemia, diabetes, anticoagulation, admission mode, baseline NIHSS and ASPECTS, type of anesthesia, and time from symptom onset to puncture. Efficacy outcomes were good functional outcome (modified Rankin Scale [mRS] 0‐3) and functional independence (mRS 0–2) at 90 days. Safety outcomes were symptomatic intracranial hemorrhages and all‐cause mortality at 90 days.ResultsAmong 385 patients, 243 (134 EVT alone and 109 IVT + EVT) were included after PS matching. There was no difference between EVT alone and IVT + EVT regarding good functional outcome (adjusted odd ratio [aOR] labeling = 1.27, 95% confidence interval [CI], 0.68–2.37, p = 0.45) and functional independence (aOR = 1.50, 95% CI, 0.79–2.85, p = 0.21). Symptomatic intracranial hemorrhage and all‐cause mortality were also similar between the two groups (aOR = 0.42, 95% CI, 0.10–1.79, p = 0.24 and aOR = 0.56, 95% CI, 0.29–1.10, p = 0.09, respectively).InterpretationIn this PS matching analysis, EVT alone seemed to lead to similar neurological recovery than IVT + EVT, with comparable safety profile. However, given our sample size and the observational nature of this study, further studies are needed to confirm these findings. ANN NEUROL 2023

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Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion

Cited by 59 publications

References 11 publications

Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke

Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke

von Willebrand Factor and Platelet Glycoprotein Ib: A Thromboinflammatory Axis in Stroke

Thrombectomy with or without Intravenous Thrombolytics in Basilar Artery Occlusion

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