Cargando…

[(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging

Intracerebral hemorrhage (ICH) is a fatal stroke subtype with significant public health impact. Although neuroinflammation is a leading cause of neurological deficits after ICH, no imaging tool is currently available to monitor brain inflammation in ICH patients. Given the role of TSPO in neuroinfla...

Descripción completa

Detalles Bibliográficos
Autores principales: Bonsack, Frederick, Foss, Catherine A., Arbab, Ali S., Alleyne, Cargill H., Pomper, Martin G., Sukumari-Ramesh, Sangeetha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826955/
https://www.ncbi.nlm.nih.gov/pubmed/29520214
http://dx.doi.org/10.3389/fnins.2018.00066
_version_ 1783302404480958464
author Bonsack, Frederick
Foss, Catherine A.
Arbab, Ali S.
Alleyne, Cargill H.
Pomper, Martin G.
Sukumari-Ramesh, Sangeetha
author_facet Bonsack, Frederick
Foss, Catherine A.
Arbab, Ali S.
Alleyne, Cargill H.
Pomper, Martin G.
Sukumari-Ramesh, Sangeetha
author_sort Bonsack, Frederick
collection PubMed
description Intracerebral hemorrhage (ICH) is a fatal stroke subtype with significant public health impact. Although neuroinflammation is a leading cause of neurological deficits after ICH, no imaging tool is currently available to monitor brain inflammation in ICH patients. Given the role of TSPO in neuroinflammation, herein we investigate whether a second-generation TSPO ligand, [(125) I]IodoDPA-713 can be used to monitor the changes in TSPO expression in a preclinical model of intracerebral hemorrhage. Male CD1 mice were subjected to ICH/Sham. The brain sections, collected at different time points were incubated with [(125) I]IodoDPA-713 and the brain uptake of [(125) I]IodoDPA-713 was estimated using autoradiography. The specificity of [(125) I]IodoDPA-713 binding was confirmed by a competitive displacement study with an unlabeled TSPO ligand, PK11195. [(125) I]IodoDPA-713 binding was higher in the ipsilateral striatum with an enhanced binding observed in the peri-hematomal brain region after ICH, whereas the brain sections from sham as well as contralateral brain areas of ICH exhibited marginal binding of [(125) I]IodoDPA-713. PK11195 completely reversed the [(125) I] IodoDPA-713 binding to brain sections suggesting a specific TSPO-dependent binding of [(125) I]IodoDPA-713 after ICH. This was further confirmed with immunohistochemistry analysis of adjacent sections, which revealed a remarkable expression of TSPO in the areas of high [(125) I]IodoDPA-713 binding after ICH. The specific as well as enhanced binding of [(125) I]IodoDPA-713 to the ipsilateral brain areas after ICH as assessed by autoradiography analysis provides a strong rationale for testing the applicability of [(125) I]IodoDPA-713 for non-invasive neuroimaging in preclinical models of ICH.
format Online
Article
Text
id pubmed-5826955
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-58269552018-03-08 [(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging Bonsack, Frederick Foss, Catherine A. Arbab, Ali S. Alleyne, Cargill H. Pomper, Martin G. Sukumari-Ramesh, Sangeetha Front Neurosci Neuroscience Intracerebral hemorrhage (ICH) is a fatal stroke subtype with significant public health impact. Although neuroinflammation is a leading cause of neurological deficits after ICH, no imaging tool is currently available to monitor brain inflammation in ICH patients. Given the role of TSPO in neuroinflammation, herein we investigate whether a second-generation TSPO ligand, [(125) I]IodoDPA-713 can be used to monitor the changes in TSPO expression in a preclinical model of intracerebral hemorrhage. Male CD1 mice were subjected to ICH/Sham. The brain sections, collected at different time points were incubated with [(125) I]IodoDPA-713 and the brain uptake of [(125) I]IodoDPA-713 was estimated using autoradiography. The specificity of [(125) I]IodoDPA-713 binding was confirmed by a competitive displacement study with an unlabeled TSPO ligand, PK11195. [(125) I]IodoDPA-713 binding was higher in the ipsilateral striatum with an enhanced binding observed in the peri-hematomal brain region after ICH, whereas the brain sections from sham as well as contralateral brain areas of ICH exhibited marginal binding of [(125) I]IodoDPA-713. PK11195 completely reversed the [(125) I] IodoDPA-713 binding to brain sections suggesting a specific TSPO-dependent binding of [(125) I]IodoDPA-713 after ICH. This was further confirmed with immunohistochemistry analysis of adjacent sections, which revealed a remarkable expression of TSPO in the areas of high [(125) I]IodoDPA-713 binding after ICH. The specific as well as enhanced binding of [(125) I]IodoDPA-713 to the ipsilateral brain areas after ICH as assessed by autoradiography analysis provides a strong rationale for testing the applicability of [(125) I]IodoDPA-713 for non-invasive neuroimaging in preclinical models of ICH. Frontiers Media S.A. 2018-02-22 /pmc/articles/PMC5826955/ /pubmed/29520214 http://dx.doi.org/10.3389/fnins.2018.00066 Text en Copyright © 2018 Bonsack, Foss, Arbab, Alleyne, Pomper and Sukumari-Ramesh. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Bonsack, Frederick
Foss, Catherine A.
Arbab, Ali S.
Alleyne, Cargill H.
Pomper, Martin G.
Sukumari-Ramesh, Sangeetha
[(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging
title [(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging
title_full [(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging
title_fullStr [(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging
title_full_unstemmed [(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging
title_short [(125) I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging
title_sort [(125) i]iododpa-713 binding to 18 kda translocator protein (tspo) in a mouse model of intracerebral hemorrhage: implications for neuroimaging
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826955/
https://www.ncbi.nlm.nih.gov/pubmed/29520214
http://dx.doi.org/10.3389/fnins.2018.00066
work_keys_str_mv AT bonsackfrederick 125iiododpa713bindingto18kdatranslocatorproteintspoinamousemodelofintracerebralhemorrhageimplicationsforneuroimaging
AT fosscatherinea 125iiododpa713bindingto18kdatranslocatorproteintspoinamousemodelofintracerebralhemorrhageimplicationsforneuroimaging
AT arbabalis 125iiododpa713bindingto18kdatranslocatorproteintspoinamousemodelofintracerebralhemorrhageimplicationsforneuroimaging
AT alleynecargillh 125iiododpa713bindingto18kdatranslocatorproteintspoinamousemodelofintracerebralhemorrhageimplicationsforneuroimaging
AT pompermarting 125iiododpa713bindingto18kdatranslocatorproteintspoinamousemodelofintracerebralhemorrhageimplicationsforneuroimaging
AT sukumarirameshsangeetha 125iiododpa713bindingto18kdatranslocatorproteintspoinamousemodelofintracerebralhemorrhageimplicationsforneuroimaging