Our research explores the pathophysiological mechanisms underlying sporadic cerebral small vessel disease (cSVD), the leading cause of vascular cognitive impairment and dementia (VCID). This condition emerges from chronic exposure to cardiovascular risk factors, such as hypertension and diabetes, which progressively damage the brain’s small blood vessels. These changes disrupt critical processes like neurovascular coupling, increase blood-brain barrier (BBB) permeability, and trigger neuroinflammation, ultimately impairing brain function.

The diverse cardiovascular risk factors involved in cSVD require us to understand the interplay between metabolic dysfunction and inflammation and how it impairs vascular health. We are especially interested in pathways regulating the glio-vascular unit, an intricate system of interactions between glial cells and cerebral blood vessels. Glial cells, including microglia, oligodendrocyte and astrocytes, are key contributors to vascular homeostasis, regulating the BBB, supporting cerebral blood flow, and promoting vascular repair.

Our experimental work ranges from cell experiments, transcriptomic analyzes to behavioural and advanced ex vivo and in vivo imaging studies. By uncovering how gliovascular signaling fails in cSVD, our research seeks to identify therapeutic strategies to protect and restore cerebro-vascular health, offering new avenues for the prevention and treatment of vascular dementia.

Current research projects

1.      Cerebrovascular dysfunction in Heart Failure with preserved Ejection fraction

This project aims to decipher the molecular mechanisms leading to vascular cognitive impairment in the presence of co-morbidities and the development of Heart Failure with preserved Ejection fraction.

2.      Impact of Angiotensin II type 1 Receptor biased agonists on cerebral circulation in health and disease

This project aims to assess the acute and chronic impact of an AT1R biased agonist on the cerebral circulation in physiological and ischemic stroke condition.

3.      Cerebral small vessel disease: an inflammatory tangle

This project aims to explore the contribution of the circulating and resident immune cell populations in the development of renal and cerebral small vessel disease using data from pre-clinical and clinical studies.

 4.      Role of Piezo1 in cerebral small vessel disease

This projects aims to uncover crucial biology downstream mechanical regulation of Piezo1 and Notch in cerebral microvasculature and its implication in cSVD. 

Lead scientist

Sebastien Foulquier