Brain regulation of pulmonary dysfunction induced by stroke

Area of Science:

• Neuroscience
• Pulmonology
• Immunology

Background:

• Ischemic stroke causes brain injury and can lead to fatal pneumonia and pulmonary dysfunction.
• The neural and molecular mechanisms linking brain infarction to lung issues remain unclear.

Purpose of the Study:

• To investigate the neural and molecular mechanisms underlying pneumonia and pulmonary dysfunction after ischemic stroke.
• To identify potential therapeutic targets for post-stroke lung complications.

Main Methods:

• Utilized whole-body plethysmography, respiratory pattern analysis, and arterial blood gas analysis to assess pulmonary function.
• Employed techniques including electrophysiology, chemogenetics, fiber photometry, ELISA, immunofluorescence, Western blotting, RT-qPCR, and histology in rodent models and clinical patients.

Main Results:

• Observed significant pneumonia and pulmonary dysfunction in middle cerebral artery occlusion rats.
• Identified decreased parasympathetic nerve function in both clinical patients and rodent models of ischemic stroke.
• Dissected a novel neuroimmune pathway involving hypothalamic PVNCaMKII neuron apoptosis, reduced DMVACh neuron activity, and subsequent upregulation of α7nAChR-HMGB1 signaling in pulmonary ganglia, leading to lung inflammation.

Conclusions:

• Acute ischemic stroke triggers apoptosis in specific hypothalamic neurons, impairing parasympathetic control of lung function.
• The α7nAChR-HMGB1 pathway in pulmonary ganglia plays a critical role in stroke-induced pneumonia and pulmonary dysfunction.
• Activating the DMVACh neuron circuit to pulmonary ganglia shows therapeutic potential for post-stroke lung complications.