A study by the Institut de Neurociències of the Universitat Autònoma de Barcelona (INc-UAB) reveals that inflammation associated with Marfan syndrome increases vulnerability to neurological diseases and complications following strokes, as demonstrated in animal models.

Published in Redox Biology, the research highlights that Marfan syndrome, a genetic disorder affecting approximately 1 in 5,000 people and primarily known for its cardiovascular complications, also has an impact on brain health. The findings show that the condition heightens the brain’s susceptibility to damage caused by reduced oxygen supply (as in heart attacks or severe hemorrhages) and raises the risk of subsequent neurological disorders. These results emphasize the importance of recognizing and managing neurological risks in Marfan patients to prevent complications and improve treatment outcomes.

Marfan syndrome affects the body’s connective tissue, which provides structural support to organs and tissues. Individuals with the condition often experience issues in the heart, eyes, blood vessels, and skeleton. If the aorta weakens or dilates, the condition can become life-threatening.

Using a mouse model of the disease, a research team led by Professor Francesc Jiménez-Altayó—researcher in the Department of Pharmacology, Therapeutics and Toxicology, the INc-UAB, and the Cardiovascular Diseases Area of the Biomedical Research Networking Center (CIBERCV)—has shown that Marfan syndrome also increases the risk of brain injury. The study also explored how sex and age affect this vulnerability.

The team compared male and female mice, both young and aged, with and without Marfan syndrome. They analyzed gene activity using RNA sequencing and evaluated biomarkers of inflammation and tissue health. In addition, they studied the structure and function of cerebral blood vessels and assessed the brain's response to temporary blood flow interruption.

The results revealed marked changes in gene expression, particularly in young males and aged females, especially involving proteins related to inflammation and tissue repair. Regardless of age or sex, Marfan mice displayed widespread brain inflammation from early stages of life, indicating a persistent imbalance in brain homeostasis.

The study uncovered disruptions in the signaling of a key regulatory protein—TGF-β (transforming growth factor beta)—as well as alterations in extracellular matrix turnover and blood vessel integrity. These changes were influenced by both sex and age.

“These mechanisms may help explain why individuals with Marfan syndrome face a higher risk of developing neurological problems, even in the absence of overt cardiovascular events,” says Gemma Manich, lead author of the paper.

“The findings underscore the need for increased awareness of potential neurological risks in people living with Marfan syndrome. At the same time, they point to possible targets for personalized treatment approaches based on age and sex,” concludes Francesc Jiménez-Altayó.

The study also involved research groups from the INc-UAB led by Professors Lydia Giménez Llort, Gemma Manich, and Clara Penas, the latter being a researcher at CIBERNED and RED-TERAV.