Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death
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 pa...
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| Format: | Article |
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SAGE Publishing
2014-03-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2013.00075 |
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| author | Nicolas Arlicot Claire Tronel Sylvie Bodard Lucette Garreau Brice de la Crompe Inge Vandevelde Denis Guilloteau Daniel Antier Sylvie Chalon |
| author_facet | Nicolas Arlicot Claire Tronel Sylvie Bodard Lucette Garreau Brice de la Crompe Inge Vandevelde Denis Guilloteau Daniel Antier Sylvie Chalon |
| author_sort | Nicolas Arlicot |
| collection | DOAJ |
| description | 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. [ 125 I]-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. |
| format | Article |
| id | doaj-art-6f497c42babc46b8bd5b0edaca857d2e |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2014-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-6f497c42babc46b8bd5b0edaca857d2e2025-01-03T01:22:54ZengSAGE PublishingMolecular Imaging1536-01212014-03-011310.2310/7290.2013.0007510.2310_7290.2013.00075Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal DeathNicolas ArlicotClaire TronelSylvie BodardLucette GarreauBrice de la CrompeInge VandeveldeDenis GuilloteauDaniel AntierSylvie ChalonExcitotoxicity 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. [ 125 I]-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.https://doi.org/10.2310/7290.2013.00075 |
| spellingShingle | Nicolas Arlicot Claire Tronel Sylvie Bodard Lucette Garreau Brice de la Crompe Inge Vandevelde Denis Guilloteau Daniel Antier Sylvie Chalon Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death Molecular Imaging |
| title | Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death |
| title_full | Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death |
| title_fullStr | Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death |
| title_full_unstemmed | Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death |
| title_short | Translocator Protein (18 kDa) Mapping with [I]-CLINDE in the Quinolinic Acid Rat Model of Excitotoxicity: A Longitudinal Comparison with Microglial Activation, Astrogliosis, and Neuronal Death |
| title_sort | translocator protein 18 kda mapping with i clinde in the quinolinic acid rat model of excitotoxicity a longitudinal comparison with microglial activation astrogliosis and neuronal death |
| url | https://doi.org/10.2310/7290.2013.00075 |
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