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Article
Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study
Xiuli Yang 1,†, Jiekang Wang 2,3,†, Yuguo Li 1,4, Mei Wan 2,3,*, Zhiliang Wei 1,4,*
1 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2 Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
4 F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD 21205, USA
* Correspondence: mwan4@jhmi.edu (M.W.); zhiliang.wei@jhu.edu (Z.W.)
† These authors contributed equally to this work.
Received: 20 November 2024; Revised: 20 December 2024; Accepted: 22 January 2025; Published: 11 February 2025
Abstract: Elevated circulating platelet-derived growth factor-BB (PDGF-BB) has been implicated in the development of various aged-related pathologies and is recognized as a potential pro-aging factor. Although numerous studies have explored the pathological roles of the PDGF-BB/PDGFRβ signaling pathway, few investigations have dissected its function in neurofunctional responses to elevated circulating PDGF-BB, primarily because in-vivo measurements are generally required to assess neurofunction. To address this knowledge gap, we characterized the vascular and metabolic responses to elevated circulating PDGF-BB in vivo using multiparametric non-invasive non-contrast MRI techniques in a conditional Pdgfb transgenic mouse model (PdgfbcTG) at 6 months of age. Results indicated that PdgfbcTG mice exhibited decreased cerebral blood flow (p = 0.025), elevated oxygen extraction (p = 0.002), and increased metabolic rate of oxygen (p = 0.035), mirroring the changes observed in human aging. The rate of change in vascular and metabolic measurements in the model mice was significantly higher (≥200.3%) compared to that of naturally aged mice. This study provides neurofunctional evidence that elevated circulating PDGF-BB accelerates neurovascular aging.
Keywords:
PDGF-BB cerebral blood flow oxygen extraction fraction cerebral metabolic rate of oxygen relaxation time diffusionReferences
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