Glial-Mediated Neuroimmune Regulation in the Brain–Heart Axis: Regional Involvement, Autonomic Imbalance and Cardiovascular Remodelling

Bidirectional communication between the brain and heart involves neuroimmune mechanisms, yet the contributions of glial responses in different brain regions to autonomic dysfunction and cardiovascular remodelling remain incompletely understood. This narrative review integrates evidence on microglial and astrocytic regulation of the brain–heart axis, focusing on autonomic brain regions and their molecular responses to cardiovascular injury. We examine how inflammatory, humoral and neural signals engage glial cells and influence neurovascular integrity, neurotransmitter homeostasis and neuronal excitability. Particular attention is given to angiotensin II signalling, purinergic pathways, NLRP3 inflammasome activation and oxidative stress as mechanisms linking glial responses to altered sympathetic–vagal balance. Across hypertension, myocardial infarction and heart failure, studies report glial alterations in multiple brain regions, with selected experiments supporting contributions to autonomic regulation and cardiovascular outcomes. However, regional involvement does not by itself establish distinct glial states or region-specific functions. We therefore distinguish regional distribution, molecular/cellular heterogeneity and causal function within a defined region, and propose a framework for testing how anatomical context, cellular state and disease stage may influence glial effects. The proposed feedback between cardiac injury, glial responses, autonomic dysfunction and cardiovascular remodelling represents an integration of evidence for individual links, rather than a directly demonstrated, fully glia-mediated causal loop. Current limitations include predominantly preclinical evidence, insufficient cell-specific causal validation and limited human translation. Integrating single-cell and spatial profiling with targeted perturbation and concurrent neural and cardiac phenotyping may clarify these relationships and inform the development of glia-directed interventions.