Endothelial progenitor cells enhance blood–brain barrier permeability in subacute stroke

Sargento-Freitas, João; Aday, Sezin; Nunes, César; Cordeiro, Miguel; Gouveia, Ana; Silva, Fernando; Machado, Carlos; Rodrigues, Bruno; Santo, Gustavo; Ferreira, Carlos; Amorim, André Ricci de; Sousa, Susana Aires de; Gomes, Ana Catarina; Castelo‐Branco, Miguel; Ferreira, Lino; Cunha, Luı́s

doi:10.1212/wnl.0000000000004801

Cited by 23 publications

(33 citation statements)

References 29 publications

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“…In fact, previous studies in mice have demonstrated a weak but significant association between angiogenesis and CBF, which is more pronounced after seven days [15] and prolongs at least up to 21 days [16]. This subacute association of angiogenesis with CBF is reinforced by recent findings associating blood-brain barrier permeability of stroke patients at seven days with good clinical outcome and more proficient EPCs [2], and are in line with our current results, where no association was found between EPCs and CBF at three months. Moreover, the interpretation of our data within these previous reports, support the notion that the hemodynamic impact of the EPCs can only be partially explained by the effect of angiogenesis on CBF [16], as could be expected considering the anatomically restricted area of neoangiogenesis in comparison to the more widespread evaluation implicated in CBF.…”

Section: Discussionmentioning

confidence: 80%

“…We isolated EPCs from 18 mL of peripheral venous blood collected in the first day and at day seven after stroke onset in accordance to previously validated protocols [1,2]. Mononuclear cells (MNC) were isolated from peripheral blood by density gradient centrifugation using Lymphoprep™ density gradient medium.…”

Section: Isolation Of Epc Sub-populationsmentioning

confidence: 99%

“…However, after the first few hours no therapy has demonstrated meaningful impact on clinical recovery. Endothelial Progenitor Cells (EPCs) are circulating cells that have emerged as a promising treatment strategy, with demonstrated in vivo capacity of promoting neovascularization and neurological improvement after stroke [1,2]. Nonetheless, their timing of action and integration within stroke hemodynamics are still unknown, which can be critical for optimization of their clinical effect.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial Progenitor Cells influence acute and subacute stroke hemodynamics

Sargento-Freitas

Aday²,

Nunes³

et al. 2018

Journal of the Neurological Sciences

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Section: Discussionmentioning

confidence: 80%

Section: Isolation Of Epc Sub-populationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Endothelial Progenitor Cells influence acute and subacute stroke hemodynamics

Sargento-Freitas

Aday²,

Nunes³

et al. 2018

Journal of the Neurological Sciences

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“…Angiogenesis plays a pivotal role in poststroke recovery; however, animal models have raised the possibility of hemorrhagic transformation as a potential complication of promoting new, immature vessels ( 14 ). Nonetheless, this link shows an apparent time-dependent response with acute disruption of the blood–brain barrier and hemorrhagic transformation in the first hours after stroke, whereas enhancing effective neoangiogenesis with improved outcomes in the subacute stage ( 8 , 15 ). These facts reinforce the need to define an optimized therapeutic window for the design of future phase III trials.…”

Section: Discussionmentioning

confidence: 99%

STROKE34 Study Protocol: A Randomized Controlled Phase IIa Trial of Intra-Arterial CD34+ Cells in Acute Ischemic Stroke

Sargento-Freitas

Pereira

Gomes³

et al. 2018

Front. Neurol.

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Rationale/aimDespite the increasing efficacy of recanalization therapies for acute ischemic stroke, a large number of patients are left with long-term functional impairment, devoid of efficacious treatments. CD34+ cells comprise a subset of bone marrow-derived mononuclear cells with the capacity to promote angiogenesis in ischemic lesions and have shown promising results in observational and in vitro studies. In this study, we aim to assess the efficacy of an autotransplant of CD34+ cells in acute ischemic stroke.Sample size estimates30 patients will be randomized for a power of 90% and alpha of 0.05 to detect a difference in 3 months infarct volume.Methods and designWe will screen 18–80 years old patients with acute ischemic stroke due to occlusion of a middle cerebral artery (MCA) for randomization. Persistent arterial occlusions, contra-indications to magnetic resonance imaging (MRI), premorbid dependency, or other severe diseases will be excluded. Treatment will involve bone marrow aspiration, selection of CD34+ cells, and their administration intra-arterially in the symptomatic MCA by angiography. Patients will be randomized for treatment at 7 (±2) days, 20 (±5 days) or sham procedure, 10 in each group.Study outcomesThe primary outcome will be infarct volume in MRI performed at 3 months. Secondary outcomes will include adverse events and multidimensional functional and neurological measures.Discussion/conclusionSTROKE34 is a PROBE design phase IIa clinical trial to assess the efficacy of intra-arterial administration of CD34+ cells 7 and 20 days after acute ischemic stroke.Trial registration (EU Clinical Trials Register)2017-002456-88.

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“… 17 18 In a later subacute stage, the BBBP relies on physiological recovery processes such as neoangiogenesis, as demonstrated in both animals 19 20 and humans. 21 Whereas the existence of this permeability process is unequivocal, its concrete evolution is not yet certain.…”

Section: Introductionmentioning

confidence: 99%

Permeability of the blood-brain barrier through the phases of ischaemic stroke and relation with clinical outcome: protocol for a systematic review

et al. 2020

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IntroductionIschaemic stroke is the most prevalent type of stroke and is characterised by a myriad of pathological events triggered by a vascular arterial occlusion. Disruption of the blood-brain barrier (BBB) is a key pathological event that may lead to fatal outcomes. However, it seems to follow a multiphasic pattern that has been associated with distinct biological substrates and possibly contrasting outcomes. Addressing the BBB permeability (BBBP) along the different phases of stroke through imaging techniques could lead to a better understanding of the disease, improved patient selection for specific treatments and development of new therapeutic modalities and delivery methods. This systematic review will aim to comprehensively summarise the existing evidence regarding the evolution of the BBBP values during the different phases of an acute ischaemic stroke and correlate this event with the clinical outcome of the patient.Methods and analysisWe will conduct a computerised search on Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include randomised controlled trials, cohort, cross-sectional and case-controlled studies on humans that quantitatively assess the BBBP in stroke. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias of the selected studies. If possible, data will be combined in a quantitative meta-analysis following the guidelines provided by Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval is not needed. All data used for this work are publicly available. The result obtained from this work will be published in a peer-reviewed journal and disseminated in relevant conferences.PROSPERO registration numberCRD42019147314.

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Endothelial progenitor cells enhance blood–brain barrier permeability in subacute stroke

Abstract: The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke.

Cited by 23 publications

References 29 publications

Endothelial Progenitor Cells influence acute and subacute stroke hemodynamics

Endothelial Progenitor Cells influence acute and subacute stroke hemodynamics

STROKE34 Study Protocol: A Randomized Controlled Phase IIa Trial of Intra-Arterial CD34+ Cells in Acute Ischemic Stroke

Permeability of the blood-brain barrier through the phases of ischaemic stroke and relation with clinical outcome: protocol for a systematic review

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