Neurovascular plasticity as a modulator of hypothalamic function

Abstract

The hypothalamus, located at the most ventral part of the brain, is the central regulator of homeostatic processes such as energy balance, autonomic functions, and reproductive regulation via the hypothalamic-pituitary-gonadal axis. The hypothalamus is organized into multiple nuclei with overlapping and distinct roles to coordinate these diverse functions. While traditional research has focused on the neuronal regulation of homeostasis, recent technological advances have broadened our understanding to include the critical roles of non-neuronal cells, particularly glial and vascular components. This review highlights emerging mechanisms by which the hypothalamic vasculature maintains brain-body homeostasis through dynamic plasticity and neurovascular signaling. We explore how metabolic cues such as nutrient flux, hormone levels, and inflammation drive vascular remodeling via coordinated actions of cells in the neuro-glial-vascular unit, including tanycytes, pericytes, and astrocytes. Understanding this intricate cellular crosstalk offers new insights into the regulation of homeostasis and reveals potential therapeutic targets for metabolic disorders.

Keywords: Extracellular matrix; Homeostasis; Hypothalamus; Neurovascular unit; Obesity; Plasticity; Vasculature.