Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam
| Autor: | Saletti, Patricia G, Mowrey, Wenzhu B, Liu, Wei, Li, Qianyun, McCullough, Jesse, Aniceto, Roxanne, Lin, I-Hsuan, Eklund, Michael, Casillas-Espinosa, Pablo M, Ali, Idrish, Santana-Gomez, Cesar, Coles, Lisa, Shultz, Sandy R, Jones, Nigel, Staba, Richard, O'Brien, Terence J, Moshé, Solomon L, Agoston, Denes V, Galanopoulou, Aristea S, EpiBioS4Rx Study Group |
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| Rok vydání: | 2023 |
| Předmět: |
Male
Traumatic Levetiracetam Epilepsy Physical Injury - Accidents and Adverse Effects levetiracetam traumatic brain injury Neurosciences Blood Proteins Neurodegenerative Traumatic Brain Injury (TBI) Rats Brain Disorders EpiBioS4Rx Study Group Seizures inflammation neuromotor recovery Brain Injuries Animals Sprague-Dawley tau HMGB1 Protein Biomarkers lateral fluid percussion injury Traumatic Head and Spine Injury |
| Zdroj: | Epilepsia open, vol 8, iss 2 |
| Popis: | ObjectiveWe used the lateral fluid percussion injury (LFPI) model of moderate-to-severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post-traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI.MethodsAdult male Sprague-Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post-LFPI, and were continuously video-EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post-LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d-to-7d neuroscore recovery, using machine learning.ResultsLow 2d plasma levels of Thr231 -phosphorylated tau protein (pTAU-Thr231 ) and S100B combined (ROC AUC = 0.7790) predicted prior craniotomy surgery (diagnostic biomarker). Levetiracetam-treated LFPI rats were differentiated from vehicle treated by the 2d-HMGB1, 2d-pTAU-Thr231 , and 2d-UCHL1 plasma levels combined (ROC AUC = 0.9394) (pharmacodynamic biomarker). Levetiracetam prevented the seizure effects on two biomarkers that predicted early seizures only among vehicle-treated LFPI rats: pTAU-Thr231 (ROC AUC = 1) and UCHL1 (ROC AUC = 0.8333) (prognostic biomarker of early seizures among vehicle-treated LFPI rats). Levetiracetam-resistant early seizures were predicted by high 2d-IFNγ plasma levels (ROC AUC = 0.8750) (response biomarker). 2d-to-7d neuroscore recovery was best predicted by higher 2d-S100B, lower 2d-HMGB1, and 2d-to-7d increase in HMGB1 or decrease in TNF (P |
| Databáze: | OpenAIRE |
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