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Updated: May 14, 2026

An In Vivo Blood-brain Barrier Permeability Assay in Mice Using Fluorescently Labeled Tracers
09:35

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Published on: February 26, 2018

CD98hc controls CNS angiogenesis and blood-brain barrier integrity through localized regulation of the systemic

Xiaoyan Hu1,2,3, Min Yu1, Shilun Yang1

  • 1State Key Laboratory of Biomedical Imaging Science and System, Guangdong-Hong Kong Joint Laboratory for Metabolic Medicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Nature Cardiovascular Research
|May 12, 2026
PubMed

Normal vascular structure and function are crucial for the homeostasis of the central nervous system (CNS), yet the regulation of CNS vasculature remains incompletely understood. Here we show that CD98 heavy chain (CD98hc), also known as SLC3A2 or 4F2hc, is essential for CNS angiogenesis and blood-brain barrier (BBB) integrity. CD98hc is selectively enriched in the CNS endothelium versus the peripheral endothelium in mice and humans. Ablation of endothelial CD98hc in mouse embryos leads to aberrant CNS angiogenesis, impaired BBB formation and cerebral hemorrhage, without affecting the peripheral vasculature. In adults, endothelial CD98hc deficiency does not impact homeostatic CNS angiogenesis but disrupts the BBB and causes neurological deficits. The mechanism involves a CNS-specific reduction in the systemic integrin-FAK pathway in endothelial cells, affecting subsequent VEGFR2 and Wnt-β-catenin pathways. Importantly, FAK activation fully rectifies the CNS vascular phenotype in CD98hc-deficient mice. These findings open promising avenues for CNS-specific vascular regulation and targeted therapy of cerebrovascular diseases.

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