The cholinergic drug galantamine ameliorates acute and subacute peripheral and brain manifestations of acute respiratory distress syndrome in mice

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute lung injury (ALI), which is a common cause of respiratory failure and high mortality in critically ill patients. Long-term mortality and cognitive impairment have been documented in ARDS patients after hospital discharge. Inflammation plays a key role in ALI/ARDS pathogenesis. Neural cholinergic signaling regulates cytokine responses and inflammation. Here, we studied the effects of galantamine, an approved cholinergic drug (for Alzheimer's disease) on ALI/ARDS severity and inflammation in mice, using a clinically relevant mouse model induced by intratracheal administration of hydrochloric acid and lipopolysaccharide. Mice were treated 30 min prior to each insult with vehicle or galantamine (4 mg/kg, i.p.). Galantamine treatment significantly decreased bronchoalveolar lavage (BAL) and serum TNF, IL-1b, and IL-6 levels, as well as BAL total protein and myeloperoxidase (MPO) and lung histopathology in ALI/ARDS mice. In addition, galantamine improved the functional state of mice with ALI/ARDS during a 10-day monitoring and attenuated lung injury and indices of brain inflammation at 10 days. These findings support further studies utilizing this approved cholinergic drug in therapeutic strategies for ALI/ARDS and its subacute sequelae.