PULMONARY arterial hypertension (PAH) may extend beyond the lungs and heart, with new findings linking the disease to brain inflammation, blood-brain barrier (BBB) dysfunction, and cognitive decline.
PAH is a progressive disorder marked by increased pressure in the pulmonary arteries, leading to right heart strain.
While traditionally viewed as a cardiopulmonary disease, patients with PAH frequently report memory problems and reduced cognitive performance, prompting researchers to investigate potential neurological involvement.
Pulmonary Arterial Hypertension Triggers Early Brain Inflammation
In this study, researchers induced PAH in male rats using monocrotaline and assessed behavioural, haemodynamic, and neurological changes after 14 days.
Animals with PAH showed clear signs of disease progression, including elevated pulmonary artery pressure and right ventricular hypertrophy.
Importantly, these physiological changes were accompanied by reduced exploratory behaviour and impaired recognition memory, indicating early cognitive dysfunction. Notably, anxiety-like behaviour was not observed, suggesting a specific effect on cognition rather than general behavioural disturbance.
Further analysis revealed significant neuroinflammation in key brain regions, including the cortex and hippocampus. This was characterised by activation of microglia and astrocytes, alongside increased levels of inflammatory markers such as tumour necrosis factor-α in the hippocampus and IL-1β in both lung and plasma.
Evidence of BBB dysfunction was also observed, demonstrated by immunoglobulin G extravasation into brain tissue.
Together, these findings suggest that PAH directly disrupts brain homeostasis, potentially driving early neurological damage.
Cognitive Decline in Pulmonary Arterial Hypertension: Implications
These findings support a growing body of evidence that PAH impacts more than the heart and lungs, affecting the central nervous system. Early neuroinflammatory responses and BBB disruption may represent key mechanisms underlying cognitive decline in PAH.
However, the study had important limitations. It was conducted in an animal model, meaning findings may not fully translate to humans. Additionally, the relatively short timeframe (14 days) captured early disease changes but not long-term neurological outcomes.
Despite these caveats, the results highlight the need for greater clinical awareness of cognitive symptoms in patients with PAH.
Future research should explore whether targeting inflammation or protecting the BBB could mitigate neurological complications.
As understanding of PAH evolves, these findings reinforce the importance of viewing the condition as a multisystem disease, with implications that reach well beyond the cardiopulmonary system.
Reference
Barbosa VM et al. Neuroinflammation, blood-brain barrier dysfunction, and cognitive decline in pulmonary arterial hypertension: an experimental study. Sci Rep. 2026; DOI:10.1038/s41598-026-44104-4.
Featured image: OhmArt on Adobe Stock
