title: Detection and quantification of remote microglial activation in rodent models of focal ischaemia using the TSPO radioligand CLINDE.
abstract: OBJECTIVE
  Neuroinflammation is involved in stroke pathophysiology and might be imaged using radioligands targeting the 18 kDa translocator protein (TSPO).
  
  
  METHODS
  We studied microglial reaction in brain areas remote from the primary lesion site in two rodent models of focal cerebral ischaemia (permanent or transient) using [125I]-CLINDE, a promising TSPO single photon emission computed tomography radioligand.
  
  
  RESULTS
  In a mouse model of permanent middle cerebral artery occlusion (MCAO), ex vivo autoradiographic studies demonstrated, besides in the ischaemic territory, accumulation of [125I]-CLINDE in the ipsilateral thalamus with a binding that progressed up to 3 weeks after MCAO. [125I]-CLINDE binding markedly decreased in animals pre-injected with either unlabelled CLINDE or PK11195, while no change was observed with flumazenil pre-treatment, demonstrating TSPO specificity. In rats subjected to transient MCAO, [125I]-CLINDE binding in the ipsilateral thalamus and substantia nigra pars reticulata (SNr) was significantly higher than that in contralateral tissue. Moreover, [125I]-CLINDE binding in the thalamus and SNr was quantitatively correlated to the ischaemic volume assessed by MRI in the cortex and striatum, respectively.
  
  
  CONCLUSIONS
  Clinical consequences of secondary neuronal degeneration in stroke might be better treated thanks to the discrimination of neuronal processes using in vivo molecular imaging and potent TSPO radioligands like CLINDE to guide therapeutic interventions.
authors.affiliation: UMR Inserm U 930, CNRS ERL 3106, Université François Rabelais de Tours, CHRU de Tours, Tours, France. nicolas.arlicot-2@etu.univ-tours.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Arlicot
authors.forename: Edwige
authors.initials: E
authors.lastname: Petit
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.forename: Didier
authors.initials: D
authors.lastname: Divoux
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bodard
authors.forename: Simon
authors.initials: S
authors.lastname: Roussel
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D017628:Microglia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: C504993:6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo(1,2-a)pyridine-3-acetamide; D019086:Bridged Bicyclo Compounds, Heterocyclic; C463819:Bzrp protein, mouse; D019275:Radiopharmaceuticals; D018079:Receptors, GABA
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