Neurobiology of diseaseDec 14, 2025

Key brain processes behind blood vessel and nerve cell problems and new combined treatment approaches

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

The neurovascular unit (NVU) is a complex system crucial for maintaining brain health.

The NVU consists of multiple cell types, including neurons, astrocytes, and endothelial cells, which work together to form the blood-brain barrier.
Traditional neuroprotective approaches have shown limited success due to a lack of consideration for the interactions within the NVU.
Six key pathological mechanisms of NVU dysfunction have been identified across various central nervous system diseases.
These mechanisms include communication disorders between cells, abnormal changes in gene regulation, and imbalances in the body's immune response and metabolism.
Emerging models and technologies are being integrated to create new research paradigms for studying the NVU.
A framework for coordinated regulatory strategies is proposed to target NVU in therapies, potentially improving treatment precision.

Simplified

The neurovascular unit (NVU) is a highly integrated multicellular complex composed of neurons, astrocytes, microglia, brain microvascular endothelial cells (BMECs), pericytes, and the extracellular matrix (ECM). It forms the structural and functional basis of the blood-brain barrier (BBB) and is pivotal for maintaining the homeostasis of the brain. Traditional neuroprotective strategies targeting individual cell types have shown limited efficacy in central nervous system (CNS) diseases, mainly due to the neglect of intricate intercellular crosstalk within the NVU. In this review, we first systematically summarize the core mechanisms by which the NVU functional unit causes NVU dysfunction in representative acute CNS injuries (ischemic/hemorrhagic stroke, traumatic brain injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, multiple sclerosis), and systemic diseases (diabetic encephalopathy, depression). Based on this, we innovatively summarize and clarify six major cross-disease pathological mechanisms of NVU dysfunction, including intercellular communication disorders, abnormal epigenetic modifications, microbiome-NVU interaction dysregulation, metabolic reprogramming dysfunction, neuroimmune-vascular coupling imbalance, and mechanical microenvironment imbalance. Additionally, we integrate emerging NVU models (co-culture systems, organoids, microfluidic chips, 3D bioprinting) with multi-omics technologies to establish a cross-scale dynamic research paradigm, and propose multicomponent coordinated regulatory strategies for NVU-targeted therapies. This framework aims to expand the understanding of NVU-centered pathological processes across diverse CNS diseases and provides a novel theoretical basis for precise therapeutic interventions, thereby bridging the gap between basic research and clinical translation.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Key brain processes behind blood vessel and nerve cell problems and new combined treatment approaches

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