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Neuroimaging of Subacute Brain Inflammation and Microstructural Changes Predicts Long-Term Functional Outcome after Experimental Traumatic Brain Injury

Missault, S., Anckaerts, C., Blockx, I., Deleye, S., Van Dam, D., Barriche, N., De Pauw, G., Aertgeerts, S., Valkenburg, F., De Deyn, P. P., Verhaeghe, J., Wyffels, L., Van der Linden, A., Staelens, S., Verhoye, M. & Dedeurwaerdere, S., 3-Oct-2018, In : Journal of Neurotrauma. 21 p.

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  • Neuroimaging of Subacute Brain Inflammation and Microstructural Changes Predicts Long-Term Functional Outcome after Experimental Traumatic Brain Injury

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DOI

  • Stephan Missault
  • Cynthia Anckaerts
  • Ines Blockx
  • Steven Deleye
  • Debby Van Dam
  • Nora Barriche
  • Glenn De Pauw
  • Stephanie Aertgeerts
  • Femke Valkenburg
  • Peter Paul De Deyn
  • Jeroen Verhaeghe
  • Leonie Wyffels
  • Annemie Van der Linden
  • Steven Staelens
  • Marleen Verhoye
  • Stefanie Dedeurwaerdere

There is currently a lack of prognostic biomarkers to predict the different sequelae following traumatic brain injury (TBI). The present study investigated the hypothesis that subacute neuroinflammation and microstructural changes correlate with chronic TBI deficits. Rats were subjected to controlled cortical impact (CCI) injury, sham surgery, or skin incision (naive). CCI-injured (n=18) and sham-operated rats (n=6) underwent positron emission tomography (PET) imaging with the translocator protein 18kDa (TSPO) radioligand [F-18]PBR111 and diffusion tensor imaging (DTI) in the subacute phase (3 weeks post-injury) to quantify inflammation and microstructural alterations. CCI-injured, sham-operated, and naive rats (n=8) underwent behavioral testing in the chronic phase (5.5-10 months post-injury): open field and sucrose preference tests, two one-week video-electroencephalogram (vEEG) monitoring periods, pentylenetetrazole (PTZ) seizure susceptibility tests, and a Morris water maze (MWM) test. In vivo imaging revealed pronounced neuroinflammation, decreased fractional anisotropy, and increased diffusivity in perilesional cortex and ipsilesional hippocampus of CCI-injured rats. Behavioral analysis revealed disinhibition, anhedonia, increased seizure susceptibility, and impaired learning in CCI-injured rats. Subacute TSPO expression and changes in DTI metrics significantly correlated with several chronic deficits (Pearson's |r|=0.50-0.90). Certain specific PET and DTI parameters had good sensitivity and specificity (area under the receiver operator characteristic [ROC] curve=0.85-1.00) to distinguish between TBI animals with and without particular behavioral deficits. Depending on the investigated behavioral deficit, PET or DTI data alone, or the combination, could very well predict the variability in functional outcome data (adjusted R-2=0.54-1.00). Taken together, both TSPO PET and DTI seem promising prognostic biomarkers to predict different chronic TBI sequelae.

Original languageEnglish
Number of pages21
JournalJournal of Neurotrauma
Publication statusE-pub ahead of print - 3-Oct-2018

    Keywords

  • diffusion tensor imaging, MRI, PET, positron emission tomography, post-traumatic epilepsy, TSPO, CONTROLLED CORTICAL IMPACT, TEMPORAL-LOBE EPILEPSY, TRANSLOCATOR PROTEIN TSPO, SPIKE-WAVE DISCHARGES, SPRAGUE-DAWLEY RATS, MORRIS WATER MAZE, POSTTRAUMATIC EPILEPSY, PET RADIOLIGAND, BINDING-AFFINITY, NERVOUS-SYSTEM

ID: 76317267