Acute Ischaemic STROKE: From LAboratory to the Patient's BED

Summary

Background: Recanalization strategies have radically changed the outcome in a significant part of stroke patients. The unpredictable occurrence of cerebral edema (CE) and hemorrhagic transformation (HT) are frequent events in patients affected by ischemic stroke, even when an effective vessel recanalization has been achieved. These complications, related with blood brain barrier (BBB) disruption, remain difficult to prevent or treat, and antagonize the beneficial effect of successful recanalization, leading to poor outcome.

Aim: to shed light on the reperfusion injury biological bases, this study aims at evaluating the effects of circulating and imaging biomarkers in relation to CE and HT both in stroke patients and in a coherent murine stroke model. A close interaction between clinical and preclinical research could lead to a broader understanding of the results deriving from the individual lines of activity, allowing a deeper interpretation of the underlying phenomena.

Methods: The clinical setting is a retrospective observational study enrolling consecutive patients with acute ischemic stroke in the anterior circulation territory, treated with reperfusion therapies, at Careggi University Hospital in Florence (Italy) from October 1, 2015 to May 31, 2020. In this cohort, the investigators will apply a new approach to assess the presence of CE and HT after stroke in CT scans, through the quantification of anatomical distortion (AD) (induced by fluid extravasation in brain tissue) at 24 hours. A large panel of blood biomarkers related to inflammation, endothelial dysfunction , and fibrin resistance to lysis, will be measured as blood samples are taken from each patient before and 24 hours after thrombolysis or thrombectomy. The role of both AD and blood biomarkers as predictors of 3 months functional outcome, assessed by modified Rankin Scale (mRS), will be estimated.

Using a translational approach the investigators will develop a new mouse model of light-induced occlusion/reperfusion of the middle cerebral artery (MCA) to better reproduce the human setting. Then, the investigators will assess functional impairment induced by stroke with and without recanalization at different time points and the investigators will assess through ex vivo experiments the insurgence of BBB alterations 24 hours after the lesion. Finally, the investigators will characterize the stroke volume and the inflammation one week after stroke.

Conditions

• Acute Ischemic Stroke
• Reperfusion Injury
• Cerebral Edema
• Hemorrhagic Transformation Due to Acute Stroke
• Animal Model

Sponsors & Collaborators

• Careggi Hospital

  collaborator OTHER

• University of Florence

  collaborator OTHER

• Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

  lead NETWORK

Principal Investigators

• Marzia Baldereschi, MD · Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-10-01

Primary Completion

2020-05-31

Completion

2023-03-31