Blood–Brain Barrier and Its Overlooked Proteoglycan Regulators
- 1Naresh K. Vashisht College of Medicine, Texas A&M University, Bryan, TX 77807, USA
- 2Houston Methodist Willowbrook Hospital, Houston, TX 77070, USA
- 3Office of Curriculum and Educational Development, Houston Methodist Academic Institute, Houston, TX 77030, USA
Abstract
The blood–brain barrier (BBB), together with associated perivascular cells, forms a key component of the neurovascular unit and constitutes a highly specialized multicellular interface that tightly regulates the movement of ions, nutrients, oxygen, metabolites, and immune cells between the circulation and the central nervous system (CNS). This selective barrier is essential for maintaining CNS homeostasis, supporting neuronal function, and protecting neural tissue from circulating toxins, pathogens, and inflammatory mediators. Disruption of BBB integrity is a hallmark of numerous neurological disorders and contributes to disease initiation and progression. Among the structural components of the BBB, the endothelial glycocalyx has emerged as a critical yet underrecognized regulator of barrier function. This carbohydrate-rich layer, composed primarily of proteoglycans, glycoproteins, and glycolipids, forms an important interface between circulating blood and the brain endothelium. Beyond serving as a physical barrier, glycocalyx proteoglycans regulate vascular permeability, mechanotransduction, leukocyte adhesion, and inflammatory signaling, thereby contributing to BBB integrity and cerebrovascular homeostasis. In this review, we discuss the architecture and function of the BBB, highlight the overlooked roles of proteoglycans in maintaining BBB integrity and regulating neurovascular function, examine their contributions to BBB dysfunction in neurological diseases, and explore emerging therapeutic approaches targeting the glycocalyx to preserve or restore BBB integrity.
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BibTeX
@article{champagne2026bloodbrain,
title = {{Blood–Brain Barrier and Its Overlooked Proteoglycan Regulators}},
author = {Rhiannon Champagne and Jordan Myers and Hannah Pearson and Kaylie Wenke and Danny Varghese and Anurag Purushothaman},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16111559},
url = {https://www.mdpi.com/2218-273X/16/11/1559},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Blood–Brain Barrier and Its Overlooked Proteoglycan Regulators
AU - Rhiannon Champagne
AU - Jordan Myers
AU - Hannah Pearson
AU - Kaylie Wenke
AU - Danny Varghese
AU - Anurag Purushothaman
PY - 2026
DA - 2026/10/26
JO - Biomolecules
DO - 10.3390/biom16111559
UR - https://www.mdpi.com/2218-273X/16/11/1559
AB - The blood–brain barrier (BBB), together with associated perivascular cells, forms a key component of the neurovascular unit and constitutes a highly specialized multicellular interface that tightly regulates the movement of ions, nutrients, oxygen, metabolites, and immune cells between the circulation and the central nervous system (CNS). This selective barrier is essential for maintaining CNS homeostasis, supporting neuronal function, and protecting neural tissue from circulating toxins, pathogens, and inflammatory mediators. Disruption of BBB integrity is a hallmark of numerous neurological disorders and contributes to disease initiation and progression. Among the structural components of the BBB, the endothelial glycocalyx has emerged as a critical yet underrecognized regulator of barrier function. This carbohydrate-rich layer, composed primarily of proteoglycans, glycoproteins, and glycolipids, forms an important interface between circulating blood and the brain endothelium. Beyond serving as a physical barrier, glycocalyx proteoglycans regulate vascular permeability, mechanotransduction, leukocyte adhesion, and inflammatory signaling, thereby contributing to BBB integrity and cerebrovascular homeostasis. In this review, we discuss the architecture and function of the BBB, highlight the overlooked roles of proteoglycans in maintaining BBB integrity and regulating neurovascular function, examine their contributions to BBB dysfunction in neurological diseases, and explore emerging therapeutic approaches targeting the glycocalyx to preserve or restore BBB integrity.
SN - 2218-273X
ER -