title: Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study.
abstract: BACKGROUND
  HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems.
  
  
  METHODS
  Dynamic [(18)F]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages.
  
  
  RESULTS
  [(18)F]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [(18)F]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA-lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different.
  
  
  CONCLUSIONS
  Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [(18)F]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat.
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, 10 Center Drive, Room 1C368, Bethesda, MD, 20814-9692, USA.
authors.forename: Dianne E
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Xuyi
authors.initials: X
authors.lastname: Yue
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, 10 Center Drive, Room 1C368, Bethesda, MD, 20814-9692, USA.
authors.forename: Wael G
authors.initials: WG
authors.lastname: Ibrahim
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, 10 Center Drive, Room 1C368, Bethesda, MD, 20814-9692, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Lentz
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, 10 Center Drive, Room 1C368, Bethesda, MD, 20814-9692, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Peterson
authors.affiliation: Molecular Imaging Program (MIP), National Cancer Institute (NCI), Bethesda, MD, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Jagoda
authors.affiliation: Chemistry Department, The University of Sydney, Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: Division of Intermural Research (DIR), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA.
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, 10 Center Drive, Room 1C368, Bethesda, MD, 20814-9692, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Reid
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health/Clinical Center, 10 Center Drive, Room 1C368, Bethesda, MD, 20814-9692, USA. hammoudd@cc.nih.gov.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications / Q000000981:diagnostic imaging / Q000821:virology*; D001931:Brain Mapping; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000000981:diagnostic imaging* / Q000209:etiology; D019788:Fluorodeoxyglucose F18 / Q000097:blood / Q000493:pharmacokinetics*; D007839:Functional Laterality; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000097:blood / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D013997:Time Factors
chemical_list: D016207:Cytokines; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D019788:Fluorodeoxyglucose F18; D017378:Quinolinic Acid