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

被引：34

作者：

Missault, Stephan ^{[1
,2
]}

Anckaerts, Cynthia ^{[2
]}

Blockx, Ines ^{[2
]}

Deleye, Steven ^{[3
]}

Van Dam, Debby ^{[5
,6
,7
,8
]}

Barriche, Nora ^{[1
]}

De Pauw, Glenn ^{[1
]}

Aertgeerts, Stephanie ^{[1
]}

Valkenburg, Femke ^{[5
,6
,7
,8
]}

De Deyn, Peter Paul ^{[5
,6
,7
,8
]}

Verhaeghe, Jeroen ^{[3
]}

Wyffels, Leonie ^{[3
,9
]}

Van der Linden, Annemie ^{[2
]}

Staelens, Steven ^{[3
]}

Verhoye, Marleen ^{[2
]}

Dedeurwaerdere, Stefanie ^{[4
]}

机构：

[1] Univ Antwerp, Fac Med & Hlth Sci, Expt Lab Translat Neurosci & Otolaryngol, Antwerp, Belgium

[2] Univ Antwerp, Fac Pharmaceut Biomed & Vet Sci, Bioimaging Lab, Antwerp, Belgium

[3] Univ Antwerp, Fac Med & Hlth Sci, Mol Imaging Ctr Antwerp, Antwerp, Belgium

[4] Univ Antwerp, Fac Med & Hlth Sci, Lab Expt Hematol, Antwerp, Belgium

[5] Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, Antwerp, Belgium

[6] Univ Groningen, Dept Neurol, Groningen, Netherlands

[7] Univ Groningen, Alzheimer Res Ctr, Groningen, Netherlands

[8] Univ Med Ctr Groningen, Groningen, Netherlands

[9] Univ Hosp Antwerp, Dept Nucl Med, Edegem, Belgium

来源：

JOURNAL OF NEUROTRAUMA | 2019年 / 36卷 / 05期

关键词：

diffusion tensor imaging; MRI; PET; positron emission tomography; post-traumatic epilepsy; TSPO; CONTROLLED CORTICAL IMPACT; TRANSLOCATOR PROTEIN TSPO; SPIKE-WAVE DISCHARGES; SPRAGUE-DAWLEY RATS; POSTTRAUMATIC EPILEPSY; BINDING-AFFINITY; NERVOUS-SYSTEM; DENTATE GYRUS; MODEL; SEIZURES;

D O I：

10.1089/neu.2018.5704

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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.

引用

页码：768 / 788

页数：21

共 76 条

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