Monocrotaline-induced pulmonary arterial hypertension in rats led to early neuroinflammatory responses, blood-brain barrier disruption, and cognitive dysfunction.
Does monocrotaline-induced pulmonary arterial hypertension cause neuroinflammation and cognitive decline in a rat model?
Experimental pulmonary arterial hypertension induces early neuroinflammation, blood-brain barrier disruption, and cognitive dysfunction, demonstrating that the disease's pathological effects extend beyond the cardiopulmonary system.
Absolute Event Rate: 65% vs 30%
p-value: p=<0.001
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.
Barbosa et al. (Fri,) conducted a other in Pulmonary arterial hypertension. Monocrotaline vs. Saline was evaluated on Pulmonary artery systolic pressure (PASP) at day 15 (p=<0.001). Monocrotaline-induced pulmonary arterial hypertension in rats led to early neuroinflammatory responses, blood-brain barrier disruption, and cognitive dysfunction.