White matter lesions (WML) are thought to contribute to vascular cognitive impairment in elderly patients. Growing evidence show that failure of myelin formation arising from the disruption of oligodendrocyte progenitor cell (OPC) differentiation is a cause of chronic vascular white matter damage. The sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P) signaling pathway regulates oligodendroglia differentiation and function, and is known to be altered in hypoxia. In this study, we measured SphK, S1P as well as markers of WML, hypoxia and OPC (NG2) in a mouse bilateral carotid artery stenosis (BCAS) model of chronic cerebral hypoperfusion. Our results indicated that BCAS induced hypoxia inducible factor (HIF)-1α, Sphk2, S1P, and NG2 up-regulation together with accumulation of WML. In contrast, BCAS mice treated with the SphK inhibitor, SKI-II, showed partial reversal of SphK2, S1P and NG2 elevation and amelioration of WML. In an in vitro model of hypoxia, SKI-II reversed the suppression of OPC differentiation. Our study suggests a mechanism for hypoperfusion-associated WML involving HIF-1α-SphK2-S1P-mediated disruption of OPC differentiation, and proposes the SphK signaling pathway as a potential therapeutic target for white matter disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuint.2016.02.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
From circuits to lifespan: translating mouse and human timelines with neuroimaging based tractography.
J Neurosci
January 2025
Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
Animal models are commonly used to investigate developmental processes and disease risk, but humans and model systems (e.g., mice) differ substantially in the pace of development and aging.
View Article and Find Full Text PDFVolumetric response after closure of a spinal CSF leak in patients with spontaneous intracranial hypotension: a multicompartmental longitudinal study.
J Neurointerv Surg
January 2025
Department of Neuroradiology, Medical Center - University of Freiburg, Freiburg, Germany
Background: Cerebrospinal fluid (CSF) loss in spontaneous intracranial hypotension (SIH) is accompanied by volume shifts between the intracranial compartments. This study investigated tricompartimental and longitudinal volume shifts after closure of a CSF leak.
Methods: Patients with SIH and suitable pre-therapeutic and post-therapeutic imaging for volumetric analysis were identified from our tertiary care center between 2020 and 2023.
A High Fat, High Sugar Diet Exacerbates Persistent Post-Surgical Pain and Modifies the Brain-Microbiota-Gut Axis in Adolescent Rats.
Neuroimage
January 2025
Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Gastroenterology, Immunology, Neuroscience (GIN) Discovery Program. Electronic address:
Persistent post-surgical pain (PPSP) occurs in a proportion of patients following surgical interventions. Research suggests that specific microbiome components are important for brain development and function, with recent studies demonstrating that chronic pain results in changes to the microbiome. Consumption of a high fat, high sugar (HFHS) diet can drastically alter composition of the microbiome and is a modifiable risk factor for many neuroinflammatory conditions.
View Article and Find Full Text PDFTractGraphFormer: Anatomically informed hybrid graph CNN-transformer network for interpretable sex and age prediction from diffusion MRI tractography.
Med Image Anal
January 2025
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:
The relationship between brain connections and non-imaging phenotypes is increasingly studied using deep neural networks. However, the local and global properties of the brain's white matter networks are often overlooked in convolutional network design. We introduce TractGraphFormer, a hybrid Graph CNN-Transformer deep learning framework tailored for diffusion MRI tractography.
View Article and Find Full Text PDFRemote neurodegeneration in the lumbosacral cord one month after spinal cord injury: a cross-sectional MRI study.
Ann Clin Transl Neurol
January 2025
Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.
Objective: To characterize structural integrity of the lumbosacral enlargement and conus medullaris within one month after spinal cord injury (SCI).
Methods: Lumbosacral cord MRI data were acquired in patients with sudden onset (<7 days) SCI at the cervical or thoracic level approximately one month after injury and in healthy controls. Tissue integrity and loss were evaluated through diffusion tensor (DTI) and T2*-weighted imaging (cross-sectional area [CSA] measurements).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!