From sympathetic storm to systemic inflammation: spatiotemporal dynamics of the brain-lung axis in neurogenic pulmonary edema.

Neurogenic pulmonary edema (NPE) is a life-threatening complication of acute central nervous system (CNS) injury, characterized by the rapid onset of hypoxemia and pulmonary fluid accumulation in the absence of underlying cardiopulmonary disease. In recent years, emerging integrative frameworks such as the "neuroimmunoaxis" and "brain-lung axis" have provided new perspectives on how CNS injury leads to systemic immune dysregulation and pulmonary dysfunction. However, critical questions remain regarding the interplay between excessive sympathetic activation, immune homeostasis disruption, and lung tissue injury. This narrative review proposes a neurotransmitter-immune-inflammatory model that integrates mechanical, adrenergic, and inflammatory pathways across the spatiotemporal evolution of NPE. We identify four progressive stages involving sympathetic storm initiation due to central autonomic network disinhibition, pulmonary vascular barrier disruption through Piezo channel activation and angiotensin II-norepinephrine synergy, inflammatory amplification from loss of the cholinergic anti-inflammatory reflex, and systemic progression involving gut-lung axis dysregulation. The model generates three testable predictions. Lesions disrupting the nucleus tractus solitarius-ventromedial hypothalamus-intermediolateral column projection should produce more severe NPE. And selective activation of TRPA1