PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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: Margaret M Zaleska; Mary Lynn T Mercado; Juan Chavez; Giora Z Feuerstein; Menelas N Pangalos; Andrew Wood Journal: Neuropharmacology Date: 2008-11-01 Impact factor: 5.250
Authors: Balázs Gulyás; Boglárka Makkai; Péter Kása; Károly Gulya; Lidia Bakota; Szilvia Várszegi; Zsuzsa Beliczai; Jan Andersson; László Csiba; Andrea Thiele; Thomas Dyrks; Tetsua Suhara; Kazutoshi Suzuki; Makato Higuchi; Christer Halldin Journal: Neurochem Int Date: 2008-10-15 Impact factor: 3.921
Authors: Filomena Mattner; David Linares Bandin; Maria Staykova; Paula Berghofer; Marie Claude Gregoire; Patrice Ballantyne; Mitchell Quinlivan; Susan Fordham; Tien Pham; David O Willenborg; Andrew Katsifis Journal: Eur J Nucl Med Mol Imaging Date: 2011-04-12 Impact factor: 9.236
Authors: P D Callaghan; C A Wimberley; G L Rahardjo; P J Berghofer; T Q Pham; T Jackson; D Zahra; T Bourdier; N Wyatt; I Greguric; N R Howell; R Siegele; Z Pastuovic; F Mattner; C Loc'h; M C Gregoire; A Katsifis Journal: Eur J Nucl Med Mol Imaging Date: 2014-09-18 Impact factor: 9.236
Authors: Cornelius K Donat; Khaled Gaber; Jürgen Meixensberger; Peter Brust; Lars H Pinborg; Henrik H Hansen; Jens D Mikkelsen Journal: Neuromolecular Med Date: 2016-03-11 Impact factor: 3.843
Authors: Benjamin A Plog; Katherine M Moll; Hongyi Kang; Jeffrey J Iliff; Matthew L Dashnaw; Maiken Nedergaard; G Edward Vates Journal: J Neurosci Methods Date: 2014-04-13 Impact factor: 2.390
Authors: William C Kreisl; Min-Jeong Kim; Jennifer M Coughlin; Ioline D Henter; David R Owen; Robert B Innis Journal: Lancet Neurol Date: 2020-11 Impact factor: 44.182
Authors: Sudhakar Selvaraj; Peter S Bloomfield; Bo Cao; Mattia Veronese; Federico Turkheimer; Oliver D Howes Journal: Schizophr Res Date: 2017-10-12 Impact factor: 4.939