TY - JOUR T1 - Neuroinflammation follow-up in a quinolinic acid rat model of excitotoxicity by translocator protein (18 kDa) mapping with CLINDE JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1796 LP - 1796 VL - 55 IS - supplement 1 AU - Nicolas Arlicot AU - Claire Tronel AU - Sylvie Bodard AU - Lucette Garreau AU - Denis Guilloteau AU - Daniel Antier AU - Sylvie Chalon Y1 - 2014/05/01 UR - http://jnm.snmjournals.org/content/55/supplement_1/1796.abstract N2 - 1796 Objectives Excitotoxicity leads to an inflammatory reaction involving TSPO overexpression 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 rat. Methods [125I]CLINDE was prepared by classical iododestannylation reaction in the presence of peracetic acid. Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of quinolinic acid (150nmol). Longitudinal follow up of neuroinflammation was measured at several time points (1,4,7,14,30,60 and 90 days post-lesion, dpl). Immunohistochemical studies for neuronal, astrocyte, and microglial specific markers were also performed on brain sections. Results Biodistribution data showed significant increase in CLINDE uptake on the injured side from 1dpl; the maximal striatal binding values evidenced a plateau between 7 and 30dpl. [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 markedly increase in microglial expression, peaking at 14dpl, astrocytic reactivity enhanced at 7 and 14dpl, whereas a prominent neuronal cell loss was observed. At 90dpl, 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. Conclusions These findings provide the possibility of a therapeutic temporal window to compare the differential effects of anti-inflammatory treatments in slowing down neurodegeneration in this rodent model, with potential applications to humans. Research Support This work was partially supported by the European Program FP7-HEALTH-2011 INMiND. ER -