Abstract
Pulmonary arterial hypertension is a progressive disorder characterized by elevated pulmonary vascular resistance and right ventricular hypertrophy. Beyond cardiopulmonary impairment, patients with PAH often present neuropsychological symptoms, suggesting central nervous system involvement. To explore this link, we evaluated cognitive, behavioral performance and neuroinflammatory changes during experimental PAH progression. Male Wistar rats received monocrotaline (60 mg/kg, intraperitoneally) or saline. After 14 days, motor activity, anxiety-like behavior, and recognition memory were assessed using the open field and novel object recognition tests. Hemodynamic and structural analyses confirmed increased pulmonary artery systolic pressure and right ventricular hypertrophy in PAH animals. These rats showed reduced exploratory activity and cognitive impairment, without anxiety-like behavior. Histological and immunofluorescence analyses revealed neuroinflammation in the cortex and hippocampus, with microglial and astrocytic changes and blood brain barrier disruption indicated by IgG extravasation. Elevated IL-1β levels were detected in the lung and plasma, while tumor necrosis factor-α was increased in the hippocampus. Plasma brain natriuretic peptide levels were also elevated. Together, these findings demonstrate that experimental PAH induces early neuroinflammatory responses and cognitive dysfunction, supporting the concept that PAH extends beyond the cardiopulmonary system to affect brain structure and memory.
Data availability
The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
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Acknowledgements
The authors thank Mr. André Benedito da Silva for support with the experiments and Ms Verônica Cristina dos Santos Lima for animal care, and Ms. Lorna O’Brien for English grammar revision. The authors declare that they have not use AI-generated work in this manuscript.
Funding
This work was supported by the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ; E-26/202.766/2018, E-26/010.001488/2019) and financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.
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VMB, RTS, CSS, TMG, and PLS were involved in the conception and design of the study. VMB, RTS, LSA, AMCC, JDS, SSC, NNR, MJCR, LCV, LFS, FLS, and PLS were involved in the acquisition of data. VMB, RTS, NNR, TMG, and PLS were involved in analyzing the results. All authors reviewed the manuscript.
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Barbosa, V.M., Santos, R.T., dos Santos de Assumpção, L. et al. Neuroinflammation, blood-brain barrier dysfunction, and cognitive decline in pulmonary arterial hypertension: an experimental study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44104-4
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DOI: https://doi.org/10.1038/s41598-026-44104-4
