Neuroinflammation in treated HIV-positive individuals: A TSPO PET study
| Autor: | Courtney A. Bishop, Paul M. Matthews, Peter Kelleher, Qi Guo, James H. Cole, Roger N. Gunn, Alan Winston, Jaime H. Vera, Nicola J. Kalk, Louise Greathead, Eugenii A. Rabiner, Adriano Boasso |
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| Přispěvatelé: | Medical Research Council (MRC) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology Pyridines 1702 Cognitive Sciences Hippocampus HIV Infections Neuropsychological Tests Brain mapping 0302 clinical medicine Positron Emission Tomography Computed Tomography Acetamides PERIPHERAL BENZODIAZEPINE-RECEPTOR Carbon Radioisotopes IN-VIVO MICROBIAL TRANSLOCATION PROTEIN 18 KDA Brain Mapping ACTIVE ANTIRETROVIRAL THERAPY biology Brain MULTIPLE-SCLEROSIS White Matter Diffusion Tensor Imaging Globus pallidus medicine.anatomical_structure Anti-Retroviral Agents RNA Viral Chemokines medicine.symptom Life Sciences & Biomedicine Adult DNA Bacterial medicine.medical_specialty Clinical Neurology CD4-CD8 Ratio Inflammation DNA Ribosomal Article White matter 03 medical and health sciences POSITRON-EMISSION-TOMOGRAPHY CEREBROSPINAL-FLUID Receptors GABA Internal medicine medicine Translocator protein Humans Neuroinflammation Science & Technology Neurology & Neurosurgery business.industry Multiple sclerosis 1103 Clinical Sciences INFECTED SUBJECTS medicine.disease IMMUNE ACTIVATION 030104 developmental biology Endocrinology biology.protein Neurosciences & Neurology Neurology (clinical) Radiopharmaceuticals 1109 Neurosciences business Biomarkers 030217 neurology & neurosurgery |
| Popis: | OBJECTIVE: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). METHODS: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [(11)C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. RESULTS: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). CONCLUSIONS: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment. |
| Databáze: | OpenAIRE |
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