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Quantification of Cerebral Vascular Architecture using Two-photon Microscopy in a Mouse Model of HIV-induced Neuroinflammation
Published on: January 12, 2016
Cerebral white matter integrity during primary HIV infection
Patrick W Wright1, Florin F Vaida, Ricardo J Fernández-de Thomas
1aDepartment of Biomedical Engineering bDepartment of Neurology, School of Medicine, St. Louis, Missouri cDepartment of Family and Preventive Medicine, UCSD, San Diego, California, USA dDepartment of Biology, University of Puerto Rico, Río Piedras, San Juan, Puerto Rico eDepartment of Psychiatry, WUSTL School of Medicine, St. Louis, Missouri fDepartment of Neurology, UCSF, San Francisco, California, USA gDivision of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria hDepartment of Radiology, WUSTL School of Medicine, St. Louis, Missouri iDepartment of Neurology, UNC, Chapel Hill, North Carolina jCenter for Imaging of Neurodegenerative Diseases, VA Medical Center, San Francisco kDepartment of Radiology and Biomedical Imaging, UCSF, San Francisco, California lDepartment of Neurology, Yale University, New Haven, Connecticut, USA. *Drs Serena S. Spudich and Beau M. Ances contributed equally to the writing of this article.
Brain white matter integrity is relatively preserved during primary HIV infection (PHI), but shows disruption linked to the blood-brain barrier and infection duration. Chronic HIV infection (CHI) significantly impacts white matter, unlike PHI.
Area of Science:
- Neuroscience
- Infectious Diseases
- Radiology
Background:
- Central nervous system inflammation and infection begin during primary HIV infection (PHI).
- The impact of these processes on white matter integrity during PHI remains unclear.
Purpose of the Study:
- To investigate white matter involvement in early HIV infection using diffusion tensor imaging (DTI).
- To assess the association between white matter integrity, blood-brain barrier disruption, and infection duration in PHI.
Main Methods:
- Prospective, cross-sectional neuroimaging study involving antiretroviral-naive PHI, chronic HIV infection (CHI), and HIV-uninfected participants.
- Diffusion tensor imaging (DTI) for white matter assessment, alongside laboratory and neuropsychometric testing.
- Region of interest and whole-brain voxelwise DTI analyses, with linear mixed-effects models for correlations.
Main Results:
- PHI participants showed preserved white matter microstructural integrity compared to controls.
- White matter integrity in PHI correlated with blood-brain barrier disruption markers (CSF/plasma albumin ratio, CSF protein).
- CHI participants exhibited significant white matter integrity loss linked to infection and inflammation biomarkers.
Conclusions:
- During PHI, white matter integrity is relatively preserved but associated with blood-brain barrier disruption and infection duration.
- Chronic HIV infection leads to substantial white matter damage, unlike the early stages.
