Modeling heart-brain interactions-on-a-chip

• Grant number: 22/16296-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): August 01, 2023
• Effective date (End): July 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Laura Nicoleti Zamproni
• Supervisor: Anna Herland
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: Karolinska Institutet, Sweden
• Associated to the scholarship: 21/14327-8 - Subarachnoid haemorrhage-in-a-chip, BP.PD

Abstract

Electrocardiographic (ECG) changes, and arrhythmias are found in 40-100% of subarachnoid hemorrhage (SAH) patients, even in a low prevalence of coronary artery disease. Cardiac arrhythmias are associated with an increased risk of prolonged hospital stay and poor outcomes or death after SAH. Therefore, investigating the brain-heart interaction after stroke is highly clinically significant. Systemic inflammatory response syndrome (SIRS) was found in approximately 50% of SAH patients on admission and 85% of patients developed SIRS within the first four days after admission. The release of proinflammatory cytokines and chemokines can be stimulated by damaged endothelial cells and astrocytes. Mounting evidence suggests that systemic inflammation may have a driving role in favoring arrhythmogenesis. Basic studies demonstrated significant direct effects of inflammatory cytokines on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels resulting in a prolonged effect on cardiomyocyte action potential duration (APD). In the original project of the post-doctoral fellowship, we aimed to build a SAH-on-a-chip model to study the role of blood-brain-barrier cells on SAH pathophysiology. Now, we want to increase the model complexity and associate two different organ-on-a-chip models to verify how cardiomyocytes behave when exposed to the SAH-on-a-chip secretome. (AU)