Cerebrovascular diseases are disorders that affect blood flow and blood supply to the brain, causing around 9 million deaths per year. Variations in cerebral circulation are found in many neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, and dementia. Recent studies suggest that abnormal flow patterns (e.g., shear stress) play an important role in jeopardising vascular endothelium morphology and function, triggering neuronal dysfunction and neurodegeneration. Yet, the mechanisms involved in the vascular-neuronal relationship and the effective treatment are poorly understood. The neurovascular unit (NVU) is a highly specialised structure composed of multiple cell types: the brain vasculature (the endothelium), perivasculature (pericytes and astrocytes), and parenchyma (astrocytes and neurons) with unique architecture. Despite decades of research, the link between blood flow alterations and brain dysfunctions remains elusive. This is mainly due to a scarcity of adequate models that recapitulate brain physiology in health and disease. To understand the interplay between flow, neurons, and the vasculature, it is necessary to study cell- cell interactions within the NVU. Understanding these links may provide insight into the disease process. Here we describe how brain flow affects vascular interaction and alters calcium activity through a human-relevant microfluidic platform known as Organs-on-a-Chip (OoC). The OoC we developed allows a more accurate simulation of the impact of blood flow alterations on vasculature and provides an exceptional opportunity to investigate cell-cell interactions. Overall, this project represents a comprehensive approach to unveiling the complexities of neuro-vascular interaction and their impact on neurological function, providing valuable insights into disease mechanisms and identifying potential avenues for therapeutic intervention.

Shear-Stress and Neuronal Pathologies: Organs-on-a-chip Model to Study Neurovascular Interaction

L. Montesi
Methodology
;
M. Tiboni
Methodology
;
R. Rauti
Supervision
2024

Abstract

Cerebrovascular diseases are disorders that affect blood flow and blood supply to the brain, causing around 9 million deaths per year. Variations in cerebral circulation are found in many neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, and dementia. Recent studies suggest that abnormal flow patterns (e.g., shear stress) play an important role in jeopardising vascular endothelium morphology and function, triggering neuronal dysfunction and neurodegeneration. Yet, the mechanisms involved in the vascular-neuronal relationship and the effective treatment are poorly understood. The neurovascular unit (NVU) is a highly specialised structure composed of multiple cell types: the brain vasculature (the endothelium), perivasculature (pericytes and astrocytes), and parenchyma (astrocytes and neurons) with unique architecture. Despite decades of research, the link between blood flow alterations and brain dysfunctions remains elusive. This is mainly due to a scarcity of adequate models that recapitulate brain physiology in health and disease. To understand the interplay between flow, neurons, and the vasculature, it is necessary to study cell- cell interactions within the NVU. Understanding these links may provide insight into the disease process. Here we describe how brain flow affects vascular interaction and alters calcium activity through a human-relevant microfluidic platform known as Organs-on-a-Chip (OoC). The OoC we developed allows a more accurate simulation of the impact of blood flow alterations on vasculature and provides an exceptional opportunity to investigate cell-cell interactions. Overall, this project represents a comprehensive approach to unveiling the complexities of neuro-vascular interaction and their impact on neurological function, providing valuable insights into disease mechanisms and identifying potential avenues for therapeutic intervention.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2750891
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact