TY - JOUR
T1 - Neuroimaging of Subacute Brain Inflammation and Microstructural Changes Predicts Long-Term Functional Outcome after Experimental Traumatic Brain Injury
AU - Missault, Stephan
AU - Anckaerts, Cynthia
AU - Blockx, Ines
AU - Deleye, Steven
AU - Van Dam, Debby
AU - Barriche, Nora
AU - De Pauw, Glenn
AU - Aertgeerts, Stephanie
AU - Valkenburg, Femke
AU - De Deyn, Peter Paul
AU - Verhaeghe, Jeroen
AU - Wyffels, Leonie
AU - Van der Linden, Annemie
AU - Staelens, Steven
AU - Verhoye, Marleen
AU - Dedeurwaerdere, Stefanie
PY - 2019/2/22
Y1 - 2019/2/22
N2 - 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.
AB - 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.
KW - diffusion tensor imaging
KW - MRI
KW - PET
KW - positron emission tomography
KW - post-traumatic epilepsy
KW - TSPO
KW - CONTROLLED CORTICAL IMPACT
KW - TEMPORAL-LOBE EPILEPSY
KW - TRANSLOCATOR PROTEIN TSPO
KW - SPIKE-WAVE DISCHARGES
KW - SPRAGUE-DAWLEY RATS
KW - MORRIS WATER MAZE
KW - POSTTRAUMATIC EPILEPSY
KW - PET RADIOLIGAND
KW - BINDING-AFFINITY
KW - NERVOUS-SYSTEM
U2 - 10.1089/neu.2018.5704
DO - 10.1089/neu.2018.5704
M3 - Article
SN - 0897-7151
VL - 36
SP - 768
EP - 788
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 5
ER -