Browsing by Author "Arlicot, N"

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    Detection and quantification of remote microglial activation in rodent models of focal ischaemia using the TSPO radioligand CLINDE.
    (Springer, 2010-12-01) Arlicot, N; Petit, E; Katsifis, A; Toutain, J; Divoux, D; Bodard, S; Roussel, S; Guilloteau, D; Bernaudin, M; Chalon, S
    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 preinjected 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. © 2010, Springer.
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    Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation
    (Springer Nature, 2008-06-07) Arlicot, N; Katsifis, A; Garreau, L; Mattner, F; Vergote, J; Duval, S; Bodard, S; Guilloteau, D; Chalon, S
    The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders. To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4'iodophenyl)-3-(N,N-diethyl) -imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion. Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5-6/group) were i.v. injected with [125I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([3H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections. In the control group, [125I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p<0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation. These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation. © 2008 Springer International Publishing