Wet and Dry Biomarkers to Predict Secondary Injury in Stroke: From Bench to Bedside - The NIMBLE Study

Summary

Infarct growth (IG), Hemorrhagic Transformation (HT) and Cerebral Edema (CE) can be considered pivotal phenomena of clinical deterioration following an acute ischemic stroke. Innovative techniques applied to neuroimaging allow these phenomena to be identified and measured more adequately than techniques and approaches commonly in use. Some circulating molecules are conceptually usable as biological markers of CE, HT, and IG. The correlation between circulating and neuroimaging biomarkers, and the investigation of neuronal structural remodeling induced by ischemia, may provide fundamental details to prevent or contrast clinical deterioration after ischemic stroke. To achieve this goal, the investigators planned to perform translational research on humans and on a novel mouse model of ischemic stroke.

More specifically, the investigators planned a clinical prospective observational study on a consecutive series of patients with acute anterior ischemic stroke either submitted or not submitted to revascularization therapies. Serum levels of several blood biomarkers related to inflammation, blood-brain barrier disruption, and reperfusion injury are analyzed in relation to CE, HT, IG, and final infarct volume, evaluated on CT/MRI images, and to 3 months functional status evaluated by the modified Rankin Scale.

In parallel, the investigators employ a newly developed experimental model of stroke and recanalization of the distal branch of the middle cerebral artery in mice to study, with advanced optical imaging techniques, the structural reorganization of neurons at the cellular and subcellular level in relation with the blood vessel extravasation (CE) and with the levels of circulating biomarkers at different time points after stroke.

The investigators will verify to what extent the animal model can reliably reproduce significant parameters that are evaluated in stroke patients, i.e. circulating biomarkers levels in relation to lesion volume and edema formation. Once validated, the data on the structural plasticity of mice shall be used to infer the mechanisms that determine the clinical deterioration due to IG, HT, and CE.

Conditions

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

Sponsors & Collaborators

• Careggi Hospital

  collaborator OTHER

• Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

  collaborator NETWORK

• University of Florence

  lead OTHER

Principal Investigators

• Cristina Sarti, MD · University of Florence, NEUROFARBA Department

• Vanessa Palumbo, MD, PhD · Careggi University Hospital

• Benedetta Piccardi, MD, PhD · Careggi University Hospital

• Anna Letizia Allegra Mascaro, PhD · Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-04-17

Primary Completion

2023-12-31

Completion

2024-12-31

Countries

• Italy

Study Locations