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Immunothrombosis in neurovascular disease.

ABSTRACT: A State of the Art lecture titled "Immunothrombosis in Neurovascular Diseases" was presented at the International Society on Thrombosis and Haemostasis Congress in 2023. Despite significant clinical advancements in stroke therapy, stroke remains a prominent contributor to both mortality and disability worldwide. Brain injury resulting from an ischemic stroke is a dynamic process that unfolds over time. Initially, an infarct core forms due to the abrupt and substantial blockage of blood flow. In the subsequent hours to days, the surrounding tissue undergoes gradual deterioration, primarily driven by sustained hypoperfusion, programmed cell death, and inflammation. While anti-inflammatory strategies have proven highly effective in experimental models of stroke, their successful translation to clinical use has proven challenging. To overcome this translational hurdle, a better understanding of the distinct immune response driving ischemic stroke brain injury is needed. In this review article, we give an overview of current knowledge regarding the immune response in ischemic stroke and the contribution of immunothrombosis to this process. We discuss therapeutic approaches to overcome detrimental immunothrombosis in ischemic stroke and how these can be extrapolated to other neurovascular diseases, such as Alzheimer's disease and multiple sclerosis. Finally, we summarize relevant new data on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress.

SUBMITTER: Denorme F

PROVIDER: S-EPMC10825058 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Immunothrombosis in neurovascular disease.

Denorme Frederik F Ajanel Abigail A Campbell Robert A RA

Research and practice in thrombosis and haemostasis 20231220 1

A State of the Art lecture titled "Immunothrombosis in Neurovascular Diseases" was presented at the International Society on Thrombosis and Haemostasis Congress in 2023. Despite significant clinical advancements in stroke therapy, stroke remains a prominent contributor to both mortality and disability worldwide. Brain injury resulting from an ischemic stroke is a dynamic process that unfolds over time. Initially, an infarct core forms due to the abrupt and substantial blockage of blood flow. In ...[more]

PMID: 38292352

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Project description:Alzheimer's disease is the commonest form of dementia, but its cause still remains elusive. It is characterized by neurodegeneration, with amyloid-beta and tau aggregation. Recently, however, the roles of the vasculature and the neurovascular unit are being highlighted as important for disease progression. In particular, there is reduced microvascular density, and altered gene expression in vascular and glial cells. Structural changes naturally impact the functioning of the neurovascular unit, and the goal of the study was to quantify the corresponding changes in vivo, non-invasively. Our assessment is based on recordings of brain oxygenation, neuronal and cardiorespiratory activities, captured by functional near-infrared spectroscopy, electroencephalogram, electrocardiogram and respiration effort, respectively. Two groups were compared: an Alzheimer's disease group (N = 19) and a control group (N = 20) of similar age. The time-series were analysed using methods that can capture multi-scale and time-varying oscillations such as the wavelet transform power and wavelet phase coherence. The Alzheimer's disease group shows a significant decrease in the power of brain oxygenation oscillations compared to the control group. There is also a significant global reduction in the phase coherence between brain oxygenation time-series. The neurovascular phase coherence around 0.1 Hz is also significantly reduced in the Alzheimer's disease group. In addition, the average respiration rate is increased in the Alzheimer's disease group compared to the control group. We show that the phase coherence between vascular and neuronal activities is reduced in Alzheimer's disease compared to the control group, indicating altered functioning of the neurovascular unit. The brain oxygenation dynamics reveals reduced power and coordination of oscillations, especially in frequency ranges that are associated with vasomotion. This could lead to reduced oxygen delivery to the brain, which could affect ATP production, and potentially reduce amyloid-beta clearance. These changes in neurovascular dynamics have potential for early diagnosis, as a marker of disease progression, and for evaluating the effect of interventions.

Project description:ImportanceCoronavirus disease 2019 patients have an increased risk of thrombotic complications that may reflect immunothrombosis, a process characterized by blood clotting, endothelial dysfunction, and the release of neutrophil extracellular traps. To date, few studies have investigated longitudinal changes in immunothrombosis biomarkers in these patients. Furthermore, how these longitudinal changes differ between coronavirus disease 2019 patients and noncoronavirus disease septic patients with pneumonia are unknown.ObjectivesIn this pilot observational study, we investigated the utility of immunothrombosis biomarkers for distinguishing between coronavirus disease 2019 patients and noncoronavirus disease septic patients with pneumonia. We also evaluated the utility of the biomarkers for predicting ICU mortality in these patients.Design setting and participantsThe participants were ICU patients with coronavirus disease 2019 (n = 14), noncoronavirus disease septic patients with pneumonia (n = 19), and healthy age-matched controls (n = 14).Main outcomes and measuresNine biomarkers were measured from plasma samples (on days 1, 2, 4, 7, 10, and/or 14). Analysis was based on binomial logit models and receiver operating characteristic analyses.ResultsCell-free DNA, d-dimer, soluble endothelial protein C receptor, protein C, soluble thrombomodulin, fibrinogen, citrullinated histones, and thrombin-antithrombin complexes have significant powers for distinguishing coronavirus disease 2019 patients from healthy individuals. In comparison, fibrinogen, soluble endothelial protein C receptor, antithrombin, and cell-free DNA have significant powers for distinguishing coronavirus disease 2019 from pneumonia patients. The predictors of ICU mortality differ between the two patient groups: soluble thrombomodulin and citrullinated histones for coronavirus disease 2019 patients, and protein C and cell-free DNA or fibrinogen for pneumonia patients. In both patient groups, the most recent biomarker values have stronger prognostic value than their ICU day 1 values.Conclusions and relevanceFibrinogen, soluble endothelial protein C receptor, antithrombin, and cell-free DNA have utility for distinguishing coronavirus disease 2019 patients from noncoronavirus disease septic patients with pneumonia. The most important predictors of ICU mortality are soluble thrombomodulin/citrullinated histones for coronavirus disease 2019 patients, and protein C/cell-free DNA for noncoronavirus disease pneumonia patients. This hypothesis-generating study suggests that the pathophysiology of immunothrombosis differs between the two patient groups.

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Immunothrombosis in neurovascular disease.

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Immunothrombosis in neurovascular disease.

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