João Sargento-Freitas1, Sezin Aday1, César Nunes1, Miguel Cordeiro1, Ana Gouveia1, Fernando Silva1, Cristina Machado1, Bruno Rodrigues1, Gustavo Cordeiro Santo1, Carlos Ferreira1, André Amorim1, Susana Sousa1, Ana Catarina Gomes1, Miguel Castelo-Branco1, Lino Ferreira2, Luís Cunha2. 1. From the Stroke Unit (J.S.-F., A.G., F.S., C.M., B.R., G.C., L.C.), Centro Hospitalar e Universitário de Coimbra; Faculdade de Medicina da Universidade de Coimbra (J.S.-F., M.C.-B., L.F., L.C.); Centro de Neurociências e Biologia Celular (J.S.-F., S.A., A.C.G., L.F.); Instituto de Ciências Nucleares Aplicadas à Saúde (C.N., M.C., C.F., A.A., M.C.-B.), Coimbra; and Genomics Unit, Biocant-Biotechnology Innovation Center (S.S., A.C.G.), Cantanhede, Portugal. 2. From the Stroke Unit (J.S.-F., A.G., F.S., C.M., B.R., G.C., L.C.), Centro Hospitalar e Universitário de Coimbra; Faculdade de Medicina da Universidade de Coimbra (J.S.-F., M.C.-B., L.F., L.C.); Centro de Neurociências e Biologia Celular (J.S.-F., S.A., A.C.G., L.F.); Instituto de Ciências Nucleares Aplicadas à Saúde (C.N., M.C., C.F., A.A., M.C.-B.), Coimbra; and Genomics Unit, Biocant-Biotechnology Innovation Center (S.S., A.C.G.), Cantanhede, Portugal. lino@uc-biotech.pt lcunha@huc.min-saude.pt.
Abstract
OBJECTIVE: To study the association among endothelial progenitor cells (EPCs), subacute blood-brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome. METHODS: We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months. Neuroimaging was performed at day 0 and 7 by MRI, including assessment of BBB permeability by dynamic contrast enhancement. EPCs were isolated from peripheral venous blood, quantified, and submitted to in vitro functional tests, including migratory and angiogenic assays. Stroke hemodynamics were evaluated serially by ultrasound. Statistical significance was set at p < 0.05. RESULTS: We included 45 patients; mean age was 70.0 ± 10.0 years. The in vitro functional properties of EPCs were associated with BBB permeability, particularly at day 7. The number of each EPC subset at both timepoints was not associated with BBB permeability. Permeability of BBB at day 7 was independently associated with improved clinical outcome (odds ratio 0.897; 95% confidence interval 0.816-0.986; p = 0.025). The EPCs (CD34+ cell subset) of patients with good clinical outcome showed 24 differentially expressed miRNAs, with a common effect on adherens junction pathway. CONCLUSIONS: The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke.
OBJECTIVE: To study the association among endothelial progenitor cells (EPCs), subacute blood-brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome. METHODS: We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months. Neuroimaging was performed at day 0 and 7 by MRI, including assessment of BBB permeability by dynamic contrast enhancement. EPCs were isolated from peripheral venous blood, quantified, and submitted to in vitro functional tests, including migratory and angiogenic assays. Stroke hemodynamics were evaluated serially by ultrasound. Statistical significance was set at p < 0.05. RESULTS: We included 45 patients; mean age was 70.0 ± 10.0 years. The in vitro functional properties of EPCs were associated with BBB permeability, particularly at day 7. The number of each EPC subset at both timepoints was not associated with BBB permeability. Permeability of BBB at day 7 was independently associated with improved clinical outcome (odds ratio 0.897; 95% confidence interval 0.816-0.986; p = 0.025). The EPCs (CD34+ cell subset) of patients with good clinical outcome showed 24 differentially expressed miRNAs, with a common effect on adherens junction pathway. CONCLUSIONS: The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke.
Authors: Sara Bernardo-Castro; João André Sousa; Ana Brás; Carla Cecília; Bruno Rodrigues; Luciano Almendra; Cristina Machado; Gustavo Santo; Fernando Silva; Lino Ferreira; Isabel Santana; João Sargento-Freitas Journal: Front Neurol Date: 2020-12-09 Impact factor: 4.003
Authors: Antía Custodia; Alberto Ouro; João Sargento-Freitas; Marta Aramburu-Núñez; Juan Manuel Pías-Peleteiro; Pablo Hervella; Anna Rosell; Lino Ferreira; José Castillo; Daniel Romaus-Sanjurjo; Tomás Sobrino Journal: Front Neurol Date: 2022-09-08 Impact factor: 4.086
Authors: João Sargento-Freitas; Anabela Pereira; André Gomes; Paula Amorim; Teresa Matos; Carla M P Cardoso; Fernando Silva; Gustavo Cordeiro Santo; César Nunes; Orlando Galego; José Carda; João Branco; Víctor Lourenço; Luís Cunha; Lino Ferreira Journal: Front Neurol Date: 2018-05-07 Impact factor: 4.003
Authors: Sara Bernardo-Castro; Inês Albino; Ángela María Barrera-Sandoval; Francesca Tomatis; João André Sousa; Emanuel Martins; Susana Simões; Miguel M Lino; Lino Ferreira; João Sargento-Freitas Journal: Life (Basel) Date: 2021-05-26