The evolution of blood–brain barrier permeability changes after stroke and its implications on clinical outcome: A systematic review and meta-analysis

Author:

Bernardo-Castro Sara12ORCID,Sousa João André1ORCID,Martins Emanuel1,Donato Helena3ORCID,Nunes César4,d’Almeida Otília C25,Castelo-Branco Miguel25ORCID,Abrunhosa Antero5,Ferreira Lino2,Sargento-Freitas João126

Affiliation:

1. Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

3. Documentation Service, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

4. Department of Medical Imaging, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

5. Coimbra Institute for Biomedical Imaging and Translational Research, Institute for Nuclear Sciences Applied to Health, University of Coimbra, Coimbra, Portugal

6. Center for Neurosciences and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Abstract

Background: Blood–brain barrier permeability (BBBp) is a key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the ischemia injury, and its clinical relevance at different timepoints post stroke. Aims: The main objective of this study is to assess BBBp evolution through stroke phases and its implications on patient outcomes. Methods: We screened PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials up to 31 December 2021. We included research quantitatively using neuroimaging to assess BBBp in stroke patients. BBBp in the different phases was evaluated by a random-effect model based on the standardized mean difference (SMD) between the ipsilateral and contralateral sides of the brain. We performed a subgroup analysis on clinical outcome, reperfusion treatment, haemorrhagic transformation, and imaging method. Results: We identified 3761 studies, of which 22 (1592 patients and 1787 evaluations) were included in our study. Overall, 17 studies reported BBBp for the hyperacute phase, 8 for the acute, 5 for the subacute, and 2 for the chronic phase. All phases were associated with increased BBBp: 0.74 (0.48–0.99), 1.68 (0.94–2.42), 1.98 (0.96–3.00), and 1.00 (0.45–1.55), respectively. An increase in BBBp was associated with hemorrhagic transformation in the hyperacute phase and with improved functional outcomes in the late subacute phase. Conclusion: BBBp is persistently increased after stroke, peaking in the acute and subacute phases. The degree of BBBp influences patient outcomes depending on stroke phase. Our findings support the clinical relevance of BBBp dynamics in stroke care.

Funder

H2020 Marie Skłodowska-Curie Actions

National Institute on Aging to the Center for Demography of Health and Aging at the University of Wisconsin–Madison

Wisconsin Alumni Research Foundation

Publisher

SAGE Publications

Subject

Neurology,Neurology (clinical)

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