Sodero Alessandro, Conti Emilia, Piccardi Benedetta, Sarti Cristina, Palumbo Vanessa, Kennedy James, Gori Anna Maria, Giusti Betti, Fainardi Enrico, Nencini Patrizia, Allegra Mascaro Anna Letizia, Pavone Francesco Saverio, Baldereschi Marzia
Neurofarba Department, University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.
Neuroscience Institute, National Research Council, Via G. Moruzzi 1, 56124, Pisa, Italy.
Transl Neurosci. 2024 Jul 12;15(1):20220344. doi: 10.1515/tnsci-2022-0344. eCollection 2024 Jan 1.
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.
脑水肿（CE）和出血性转化（HT）在急性缺血性卒中（AIS）患者中很常见且不可预测，即使已实现有效的血管再通也是如此。这些与血脑屏障（BBB）破坏相关的并发症仍然难以预防或治疗，可能会抵消再通的有益效果，并导致不良预后。这项转化研究的目的是评估循环和成像生物标志物与卒中患者随后发生的CE和HT之间的关联，其双重目的是研究可能的预测因素以及这些事件和功能结局背后的分子动力学。同时，临床前研究将开发一种新的大脑中动脉（MCA）闭塞和再通小鼠模型，以探索血脑屏障的改变及其对组织的潜在有害影响。该研究的临床部分基于单中心观察性设计，纳入2015年10月1日至2020年5月31日接受再通治疗的前循环区域连续AIS患者。该研究将采用对常规CT扫描的创新评估：事实上，我们将通过量化解剖变形（AD）（一种CE和HT的测量方法）来评估和量化卒中后24小时CT扫描中CE和HT的存在情况。我们将研究AD与几种炎症和细胞外基质的血液生物标志物之间的关系，以及3个月时的功能结局。同时，我们将采用新开发的卒中再通小鼠模型，研究卒中发作后24小时血脑屏障变化的出现情况。临床研究与临床前研究之间的密切互动可以增强我们对每个研究分支结果的理解，从而更深入地解释AIS再通治疗后再灌注损伤的潜在机制。
