title: Translocator protein (18 kDa) mapping with [125I]-CLINDE in the quinolinic acid rat model of excitotoxicity: a longitudinal comparison with microglial activation, astrogliosis, and neuronal death.
abstract: Excitotoxicity leads to an inflammatory reaction involving an overexpression of: translocator protein 18 kDa (TSPO) in cerebral microglia and astrocytes. Therefore, we performed ex vivo explorations with [125]-CLINDE, a TSPO-specific radioligand, to follow the time course of TSPO expression, in parallel with lesion progression, over 90 days after induction of cerebral excitotoxicity in rats intrastriatally injected with quinolinic acid. Biodistribution data showed a significant increase in CLINDE uptake on the injured side from 1 days postlesion (dpl); the maximal striatal binding values evidenced a plateau between 7 and 30 dpl. [125I]-CLINDE binding was displaced from the lesion by PK11195, suggesting TSPO specificity. These results were confirmed by ex vivo autoradiography. Combined immunohistochemical studies showed a marked increase in microglial expression in the lesion, peaking at 14 dpl, and astrocytic reactivity enhanced at 7 and 14 dpl, whereas a prominent neuronal cell loss was observed. At 90 dpl, CLINDE binding and immunoreactivity targeting activated microglia, astrogliosis, and neuronal cell density returned to a basal level. These results show that both neuroinflammation and neuronal loss profiles occurred concomitantly and appeared to be transitory processes. These findings provide the possibility of a therapeutic temporal window to compare the differential effects of antiinflammatory treatments in slowing down neurodegeneration in this rodent model, with potential applications to humans.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Arlicot
authors.forename: Claire
authors.initials: C
authors.lastname: Tronel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bodard
authors.forename: Lucette
authors.initials: L
authors.lastname: Garreau
authors.forename: Brice
authors.initials: B
authors.lastname: de la Crompe
authors.forename: Inge
authors.initials: I
authors.lastname: Vandevelde
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Daniel
authors.initials: D
authors.lastname: Antier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000493:pharmacokinetics; D016923:Cell Death / Q000187:drug effects*; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D017628:Microglia / Q000187:drug effects*; D057054:Molecular Imaging / Q000379:methods*; D009498:Neurotoxins / Q000737:chemistry / Q000493:pharmacokinetics; D017378:Quinolinic Acid / Q000633:toxicity*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C504993:6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo(1,2-a)pyridine-3-acetamide; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007457:Iodine Radioisotopes; D009498:Neurotoxins; D018079:Receptors, GABA; D017378:Quinolinic Acid