Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

The neuropathology following traumatic brain injury (TBI) is poorly understood. From the primary biomechanical injury, secondary injuries develop, including neuro-inflammatory processes. These secondary injuries are regarded as a potential targets for treatment and diagnostics. The translocator protein 18 kDa (TSPO) is robustly upregulated in response to brain injury, making it a suitable biomarker for glia activation and the neuro-inflammatory response. Second-generation radioligands of TSPO, such as [123I]CLINDE, offer higher affinity and signal-to-noise ratio compared to PK11195, the prototypical ligand. Applicability of [123I]CLINDE was demonstrated in both neurodegenerative disease models and patient studies and therefore demonstrate the translational value of this tracer. We therefore investigated TSPO expression in a rat model of TBI with [123I]CLINDE , a selective and clinically relevant TSPO-radioligand.
Adult Sprague-Dawley rats were subjected to moderate Controlled-Cortical-Impact injury (CCI, n=5 per group). Sham (n=5), craniotomy (n=3), and naïve animals (n=3) served as different control groups. Animals were sacrificed at 6h, 24h, 72h, and 28 days post-surgery, and TSPO expression was assessed in brain section employing [123I]CLINDE in vitro autoradiography.
From 24 h to 28 d post-surgery, injured animals exhibited a marked and time-dependent increase of binding in the ipsilateral motor, somatosensory and parietal cortex, as well as in the hippocampus and thalamus. Furthermore, binding was significantly elevated in the contralateral motor cortex following TBI. Craniotomy also caused a significant increase in [123I]CLINDE binding per se. Radioligand binding was consistent with an increase in TSPO mRNA expression and OX-42 immunoreactivity at the contusion site.
In conclusion, this study demonstrates the applicability of [123I]CLINDE for brain regional and quantitative assessment of neuro-inflammatory activity in experimental models of TBI.