gms | German Medical Science

60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

26. - 28.08.2015, Berlin

Robust increase of the translocator protein 18 kDa (TSPO), demonstrated with the selective radioligand [123I]CLINDE, in an adult rat model of Traumatic Brain Injury

Meeting Abstract

  • corresponding author presenting/speaker Cornelius K. Donat - Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Copenhagen, Denmark; Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, Denmark
  • Khaled Gaber - Leipzig University Hospital, Department of Neurosurgery, Leipzig, Germany
  • Jürgen Meixensberger - Leipzig University Hospital, Department of Neurosurgery, Leipzig, Germany
  • Peter Brust - Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, Germany
  • Lars H. Pinborg - Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Copenhagen, Denmark
  • Jens D. Mikkelsen - Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Copenhagen, Denmark

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP19

doi: 10.3205/15dgnn43, urn:nbn:de:0183-15dgnn436

Published: August 25, 2015

© 2015 Donat et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Question: Traumatic brain injury (TBI) can cause long-term disability by mechanisms not fully elucidated. Neuroinflammation is part of the secondary injury cascade, and is therefore regarded as a potential target for treatment and diagnostics, employing molecular imaging techniques. TSPO, a protein in the mitochondrial membrane, is robustly upregulated in response to injury and neuroinflammation, making it a suitable biomarker. We therefore hypothesize that TSPO is time-dependently upregulated after TBI. This was investigated in a rat model of TBI, employing the TSPO-selective and clinically relevant radioligand [123I]CLINDE.

Methods: Adult male Sprague-Dawley rats were randomized into four groups (survival time: 6, 24, 72 h and 28 d). Animals were anaesthetized and subjected to either sham injury, craniotomy or mild-to-moderate (2 mm impact depth at 4 m/sec) Controlled Cortical Impact injury (CCI). Drug/surgery-naļve animals were included in the study. Frozen coronal sections were cut and TSPO binding was assessed with in vitro autoradiography in the vicinity of the injury (M1 motor cortex, 3.5 mm posterior, 4.0 mm lateral to bregma)

Results: Binding of [123I]CLINDE was nearly uniform and displaceable (10 µMol/L PK11195) in the brains of naļve and sham-operated animals.

At 24 h, injured animals exhibited a significant increase in binding in the whole ipsilateral hemisphere (49%) and M1 cortex (201%). Interestingly, CCI also resulted in an elevated binding in the contralateral M1 cortex (38%). [123I]CLINDE binding was maximally increased at 72 h after CCI in the whole ipsilateral hemisphere (368 %) and M1 cortex (1076%). Again, TBI significantly increased binding in the contralateral whole hemisphere (29%) and M1 cortex (32%).

Surprisingly, craniotomy without TBI, produced a significant increase in TSPO at 24 h in the ipsilateral M1 cortex (42%) and at 72h in the ipsilateral hemisphere (232%) and M1 cortex (598%).

At 6 h and 28 d, [123I]CLINDE binding was not significantly different between the groups.

Conclusions: [123I]CLINDE binding, reflecting TSPO, was significantly increased after experimental TBI, which corresponds to the time-course of the inflammatory response. This makes [123I]CLINDE a suitable radiotracer for the assessment of brain injury in TBI and the monitoring of anti-inflammatory (pharmaco)therapies.