[18F]DPA-714 PET Imaging Reveals Global Neuroinflammation in Zika Virus-Infected Mice.

Purpose: The association of Zika virus (ZIKV) infection and development of neurological sequelae require a better understanding of the pathogenic mechanisms causing severe disease. The purpose of this study was to evaluate the ability and sensitivity of positron emission tomography (PET) imaging usi...

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Publicado en:Molecular Imaging & Biology Vol. 20; no. 2; pp. 275 - 284
Autores principales: Kuszpit, Kyle, Hollidge, Bradley S., Zeng, Xiankun, Stafford, Robert G., Daye, Sharon, Zhang, Xiang, Basuli, Falguni, Golden, Joseph W., Swenson, Rolf E., Smith, Darci R., Bocan, Thomas M.
Formato: pictorial research tables/charts Journal Article
Publicado: Springer Nature Apr2018
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: Molecular Imaging & Biology
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      dt: Apr2018
      vid: 20
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11307-017-1118-2
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        atl: [18F]DPA-714 PET Imaging Reveals Global Neuroinflammation in Zika Virus-Infected Mice.
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        au:
          Kuszpit, Kyle
          Hollidge, Bradley S.
          Zeng, Xiankun
          Stafford, Robert G.
          Daye, Sharon
          Zhang, Xiang
          Basuli, Falguni
          Golden, Joseph W.
          Swenson, Rolf E.
          Smith, Darci R.
          Bocan, Thomas M.
        affil: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425, Porter St., Ft. Detrick, 21702, Frederick, MD, USA
      sug:
        subj:
          Inflammation
          Tomography, Emission-Computed
          Heterocyclic Compounds
          Brain Pathology
          Fluorine Radioisotopes
          RNA Metabolism
          Pathologic Processes Pathology
          Pathologic Processes Blood
          Inflammation Blood
          Mice
          Female
          Inflammation Pathology
          Brain
          Receptors, Cell Surface Metabolism
          Animal Studies
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Funding Source
          Female
      ab: Purpose: The association of Zika virus (ZIKV) infection and development of neurological sequelae require a better understanding of the pathogenic mechanisms causing severe disease. The purpose of this study was to evaluate the ability and sensitivity of positron emission tomography (PET) imaging using [18F]DPA-714, a translocator protein (TSPO) 18 kDa radioligand, to detect and quantify neuroinflammation in ZIKV-infected mice.Procedures: We assessed ZIKV-induced pathogenesis in wild-type C57BL/6 mice administered an antibody to inhibit type I interferon (IFN) signaling. [18F]DPA-714 PET imaging was performed on days 3, 6, and 10 post-infection (PI), and tissues were subsequently processed for histological evaluation, quantification of microgliosis, and detection of viral RNA by in situ hybridization (ISH).Results: In susceptible ZIKV-infected mice, viral titers in the brain increased from days 3 to 10 PI. Over this span, these mice showed a two- to sixfold increase in global brain neuroinflammation using [18F]DPA-714 PET imaging despite limited, regional detection of viral RNA. No measurable increase in ionized calcium binding adaptor molecule 1 (Iba-1) expression was noted at day 3 PI; however, there was a modest increase at day 6 PI and an approximately significant fourfold increase in Iba-1 expression at day 10 PI in the susceptible ZIKV-infected group relative to controls.Conclusions: The results of the current study demonstrate that global neuroinflammation plays a significant role in the progression of ZIKV infection and that [18F]DPA-714 PET imaging is a sensitive tool relative to histology for the detection of neuroinflammation. [18F]DPA-714 PET imaging may be useful in dynamically characterizing the pathology associated with neurotropic viruses and the evaluation of therapeutics being developed for treatment of infectious diseases.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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