Impact of mechanical ventilation on oxidative stress, neuroinflammation, memory and anxiety related behavior: insights from an experimental model

Mechanical ventilation is an essential intervention for patients with acute respiratory failure. However, ventilatory strategies with high tidal volumes can be harmful, and are strongly associated with ventilator-induced lung injury. Growing evidence suggests that ventilator-induced lung injury may also trigger oxidative stress and contribute to systemic inflammation and neuronal impairment, particularly in regions such as the hippocampus, which plays a fundamental role in cognitive functions. Investigate the impact of high tidal volume mechanical ventilation on anxiety-related behaviors, memory, inflammation, and oxidative stress in the central nervous system of male Wistar rats. Animals were assigned to three groups: spontaneous ventilation, mechanical ventilation with 6 mL/kg, and mechanical ventilation with 12 mL/kg. Ventilated animals underwent volume-controlled ventilation for 180 minutes. Our findings showed that high tidal volume ventilation led to a marked influx of inflammatory cells, increased oxidative stress, and structural damage in the lungs. These pulmonary alterations were accompanied by elevated levels of oxidative markers and pro-inflammatory cytokines in the hippocampus and amygdala. Ventilated animals showed significant deficits in memory-related tasks, and increased anxiety related behaviors. The relationship between oxidative stress, neuroinflammation, and behavioral changes validates the hypothesis that the ventilator-induced lung injury effects extend beyond the lungs, impairing brain function and leading to cognitive deficits. This study advances current knowledge by showing that even short periods of mechanical ventilation can trigger early neurobehavioral changes. These findings underscore the need for protective ventilation strategies to minimize the systemic effects of mechanical ventilation. • High tidal volume ventilation caused oxidative stress in the hippocampus. • High tidal volume ventilation increased inflammation in the hippocampus and amygdala • Cognitive and behavioral deficits followed brain inflammatory changes. • Oxidative stress and inflammation may link lung damage to brain effects.