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Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy.

ABSTRACT: Using standard techniques during mechanical thrombectomy, the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (NCT03153683) isolates intracranial arterial blood distal to the thrombus and proximal systemic blood in the carotid artery. We augmented the current protocol to study leukocyte subpopulations both distal and proximal to the thrombus during human stroke (n = 16 patients), and from patients with cerebrovascular disease (CVD) undergoing angiography for unrelated conditions (e.g. carotid artery stenosis; n = 12 patients). We isolated leukocytes for flow cytometry from small volume (<1 mL) intracranial blood and systemic blood (5-10 mL) to identify adaptive and innate leukocyte populations, in addition to platelets and endothelial cells (ECs). Intracranial blood exhibited significant increases in T cell representation and decreases in myeloid/macrophage representation compared to within-patient carotid artery samples. CD4⁺ T cells and classical dendritic cells were significantly lower than CVD controls and correlated to within-patient edema volume and last known normal. This novel protocol successfully isolates leukocytes from small volume intracranial blood samples of stroke patients at time of mechanical thrombectomy and can be used to confirm preclinical results, as well as identify novel targets for immunotherapies.

SUBMITTER: Shaw BC

PROVIDER: S-EPMC8795221 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy.

Shaw Benjamin C BC Maglinger G Benton GB Ujas Thomas T Rupareliya Chintan C Fraser Justin F JF Grupke Stephen S Kesler Melissa M Gelderblom Mathias M Pennypacker Keith R KR Turchan-Cholewo Jadwiga J Stowe Ann M AM

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20210711 2

Using standard techniques during mechanical thrombectomy, the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (NCT03153683) isolates intracranial arterial blood distal to the thrombus and proximal systemic blood in the carotid artery. We augmented the current protocol to study leukocyte subpopulations both distal and proximal to the thrombus during human stroke (n = 16 patients), and from patients with cerebrovascular disease (CVD) undergoing angiography for unrelated c ...[more]

PMID: 34250820

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Project description:BackgroundEmergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.MethodsThe blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11.ResultsIncreased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = -0.409) and intracranial (p=0.011; r = -0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume.ConclusionsThe current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.

Project description:BackgroundMechanical thrombectomy (MT) has been proven as an effective and safe therapy for patients with acute ischemic stroke from large vessel occlusion. However, there is still a controversial topic about post-procedural management including blood pressure (BP).MethodsA total of 294 patients who received MT in Second Affiliated Hospital of Soochow University from April 2017 to September 2021 were included consecutively. The association of blood pressure parameters (BPV and hypotension time) with poor functional outcome was evaluated using logistic regression models. Meanwhile, the effects of BP parameters on mortality was analyzed using cox proportional hazards regression models. Furthermore, the corresponding multiplicative term was added to the above models to study the interaction between BP parameters and CS.ResultsTwo hundred ninety four patients were included finally. The mean age was 65.5 years. At the 3-month follow-up, 187(61.5%) had poor functional outcome and 70(23.0%) died. Regardless of the CS, BP CV is positively associated with poor outcome. Hypotension time was negatively associated with poor outcome. We conducted a subgroup analysis according to CS. BPV was significantly associated with mortality at 3-month and displayed a trend toward poor outcome for patients with poor CS only. The interaction between SBP CV and CS with respect to mortality after adjusting for confounding factors was statistically significant (P for interaction = 0.025) and the interaction between MAP CV and CS with respect to mortality after multivariate adjustment was also statistically significant (P for interaction = 0.005).ConclusionIn MT-treated stroke patients, higher BPV in the first 72 h is significantly associated with poor functional outcome and mortality at 3-month regardless of CS. This association was also found for hypotension time. Further analysis showed CS modified the association between BPV and clinical prognosis. BPV displayed a trend toward poor outcome for patients with poor CS.

Project description:ObjectivesOptimal periprocedural blood pressure (BP) management during mechanical thrombectomy (MT) for acute ischaemic stroke is still controversial. The aim of this study was to investigate the association between intraprocedural BP variability (BPV) and outcomes in patients with large vessel occlusion (LVO) following MT with general anaesthesia.DesignA prospective observational cohort study.SettingThis study was conducted in a single tertiary hospital of Hangzhou in Zhejiang province.ParticipantsA total of 141 patients with LVO treated with MT were finally included between January 2018 and September 2020.Main outcome measuresIntraprocedural BP was recorded every 5 min throughout the procedure. BPV was measured as SD, coefficient of variation (CV), max-min (RANGE) and successive variation. Haemorrhagic transformation was assessed on 24-hour CT images according to European Cooperative Acute Stroke Study III trial. Poor functional outcome was defined as 90-day modified Rankin Scale score 3-6. Binary logistic regression analysis was used to investigate the association of BPV parameters with the incidence of parenchymal haemorrhage (PH) and poor functional outcome.ResultsAfter controlling for age, female, history of smoking, hypertension and atrial fibrillation, baseline National Institutes of Health Stroke Scale, baseline systolic BP (SBP), baseline Alberta Stroke Program Early CT Score, bridging thrombolysis and times of retrieval attempts, the results demonstrated that intraprocedural SBPRANGE (OR 1.029; 95% CI 1.003 to 1.055; p=0.027), SBPSD (OR 1.135; 95% CI 1.023 to 1.259; p=0.017) and SBPCV (OR 1.189; 95% CI 1.053 to 1.342; p=0.005) were independently associated with poor functional outcome. However, the independent association between intraprocedural BPV and PH at 24 hours has not been established in this study.ConclusionsIncreased intraprocedural BPV was more likely to have poor functional outcome in patients with LVO following MT with general anaesthesia. This finding indicates that special precautions should be taken to minimise BP fluctuation during procedure.

Dataset Information

Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy.

Publications

Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy.

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