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<p>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&#xa0;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.</p>

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Neuroinflammation, blood-brain barrier dysfunction, and cognitive decline in pulmonary arterial hypertension: an experimental study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月3日

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  • Victória Marques Barbosa,
  • Renata Trabach Santos,
  • Leonardo dos Santos de Assumpção,
  • Aryella Maryah Couto Correa,
  • Sabrina Sodré de Souza Serra,
  • Louise Caroline Vitorino,
  • Samantha da Silva Christovam,
  • Johnatas Dutra Silva,
  • Paula Rodrigues Pereira,
  • Nazareth de Novaes Rocha,
  • Maria Julia Cadrieskt Ribeiro,
  • Lucas Ferreira dos Santos,
  • Felipe Simões Lemos,
  • Patricia Rieken Macedo Rocco,
  • Cynthia dos Santos Samary,
  • Tatiana Maron-Gutierrez,
  • Pedro Leme Silva

摘要

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.