Neurovascular Unit Dysfunction and Neural Barrier Pathology in Dysautonomia: Molecular Links to Cardiovascular Autonomic Failure.

Cardiovascular autonomic failure arises from lesions across central nuclei, peripheral nerves, and autonomic ganglia. This review examines whether dysfunction of the neurovascular unit and neural barriers contributes to that failure. The clearest evidence comes from rodent models of hypertension and heart failure. Increased permeability in the PVN, NTS, and RVLM develops alongside sympathetic activation and impaired baroreflex control. Angiotensin II and inflammation appear to affect endothelial transport and junctional integrity. Exercise and interventions directed at these pathways improve barrier function together with autonomic control. Peripheral evidence is less direct. Diabetes and inflammatory neuritis alter the blood-nerve barrier, but most experiments examine somatic or sensory nerves and do not establish causation in cardiovascular autonomic neuropathy. Autonomic ganglia also differ in normal vascular permeability, which precludes treating them as uniform extensions of the blood-nerve barrier. Human studies show altered barrier measurements in heart failure and synucleinopathies, yet rarely pair regional permeability with validated autonomic tests. Neural barrier dysfunction may contribute to dysautonomia in defined anatomical and clinical settings. Its importance remains uncertain outside the pathways examined directly, and future studies should relate regional barrier changes to autonomic function over time.