Acute ischemic STROKE – From laboratory to the Patient´s BED (STROKELABED): A translational approach to reperfusion injury. Study Protocol

Year: 2024

Authors: Sodero A., Conti E., Piccardi B., Sarti C., Palumbo V., Kennedy J., Gori AM., Giusti B., Fainardi E., Nencini P., Mascaro ALA., Pavone FS., Baldereschi M.

Autors Affiliation: Careggi Univ Hosp, Stroke Unit, Largo Brambilla 3, I-50134 Florence, Italy; Univ Florence, Neurofarba Dept, Viale G Pieraccini 6, I-50139 Florence, Italy; CNR, Neurosci Inst, Via G Moruzzi 1, I-56124 Pisa, Italy; European Lab Nonlinear Spect, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Phys & Astron, I-50019 Sesto Fiorentino, Italy; Univ Oxford, John Radcliffe Hosp, Acute Multidisciplinary Imaging & Intervent Ctr, Radcliffe Dept Med, Oxford, England; Univ Florence, Azienda Osped Univ Careggi, Atherothrombot Dis Ctr, Dept Expt & Clin Med, Largo Brambilla 3, I-50134 Florence, Italy; Univ Florence, Dept Expt & Clin Biomed Sci Mario Serio, Neuroradiol Unit, Viale Morgagni 50, I-50134 Florence, Italy; CNR, Natl Inst Opt, I-50019 Sesto Fiorentino, Italy; CNR, Neurosci Inst, Via Madonna Piano 10, I-50019 Sesto Fiore ntino, Italy.

Abstract: Cerebral edema (CE) and hemorrhagic transformation (HT) are frequent and unpredictable events in patients with acute ischemic stroke (AIS), even when an effective vessel recanalization has been achieved. These complications, related to blood-brain barrier (BBB) disruption, remain difficult to prevent or treat and may offset the beneficial effect of recanalization, and lead to poor outcomes. The aim of this translational study is to evaluate the association of circulating and imaging biomarkers with subsequent CE and HT in stroke patients with the dual purpose of investigating possible predictors as well as molecular dynamics underpinning those events and functional outcomes. Concurrently, the preclinical study will develop a new mouse model of middle cerebral artery (MCA) occlusion and recanalization to explore BBB alterations and their potentially harmful effects on tissue. The clinical section of the study is based on a single-center observational design enrolling consecutive patients with AIS in the anterior circulation territory, treated with recanalization therapies from October 1, 2015 to May 31, 2020. The study will employ an innovative evaluation of routine CT scans: in fact, we will assess and quantify the presence of CE and HT after stroke in CT scans at 24 h, through the quantification of anatomical distortion (AD), a measure of CE and HT. We will investigate the relationship of AD and several blood biomarkers of inflammation and extracellular matrix, with functional outcomes at 3 months. In parallel, we will employ a newly developed mouse model of stroke and recanalization, to investigate the emergence of BBB changes 24 h after the stroke onset. The close interaction between clinical and preclinical research can enhance our understanding of findings from each branch of research, enabling a deeper interpretation of the underlying mechanisms of reperfusion injury following recanalization treatment for AIS.

Journal/Review: TRANSLATIONAL NEUROSCIENCE

Volume: 15 (1)      Pages from: 20220344-1  to: 20220344-8

More Information: This research was funded by Fondazione Cassa di Risparmio di Firenze, Grant number codice SIME 2018/1179 id#24055 for the project Ictus ischemico acuto: dal laboratorio al letto del malato. Studio di biomarcatori ematici e dineuroimaging come predittori diedema cerebrale, estensionedella lesione ischemica e dell’outcome funzionale.
KeyWords: stroke; cerebral edema; hemorrhagic transformation; reperfusion injury; biomarkers; translational stroke research
DOI: 10.1515/tnsci-2022-0344


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