PET Imaging of Neuroinflammation as a Biomarker of Post-traumatic Epilepsy
Abstract number :
3.225
Submission category :
2. Translational Research / 2C. Biomarkers
Year :
2024
Submission ID :
111
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Mohit Javalgekar, MS – Monash University
Bianca Jupp, PhD – Monash University
Peravina Thergarajan, PhD – Monash University
Juliana Silva, PhD – Monash University
Emma Braine, PhD – Monash University
Lucy Vivash, PhD – Monash University
Robert Brakljaca, PhD – Monash University
Stephanie Dedeurwaerdere, Senior Director – UCB Pharma
Mohammad Haskali, PhD – Peter maccallum cancer center
Terence J O'Brien, MBBS MD – School of Translational Medicine, Monash University, The Alfred Centre
Nigel Jones, Professor – Monash University
David Wright, Associate Professor – Monash University
Idrish Ali, PhD – Monash University
Rationale: Literature suggests that inflammation could drive epileptogenesis and behavioural impairment after traumatic brain injury (TBI). To determine the potential of neuroinflammation as a predictive biomarker for post-traumatic epilepsy (PTE), we measured brain inflammation using in vivo Positron Emission Tomography (PET) imaging of translocator protein (TSPO) in a rat model of TBI and assessed whether these imaging parameters related to epilepsy and neurobehavioral outcomes.
Methods: TBI was induced by fluid percussion injury surgery in SD rats (n= 39). At 1-week and 1-month time points, brain TSPO level was measured using a 60-minute PET acquisition after IV injection of the [18F]-FBR and a CT scan for attenuation correction and a T2 weighted MRI for co-registering PET. At 5 months post-TBI, neurobehavioral tests including the Morris water maze test were performed. EEG recording was performed at 6 months post-TBI to identify epileptic animals (n=7).
Results: The cortical region at one week (p< 0.0001), and one month after TBI (p< 0.0001), the hippocampus at one month (p< 0.0001), and the thalamus (p< 0.0001), at one month all showed a significant elevation of PET Standardised Uptake Value (SUV) for TSPO in TBI rats compared to sham rats. Remarkably, one month after TBI, TSPO levels were higher in the thalamus (p=0.029) and hippocampal regions (p=0.020) of TBI non-epileptic (TBI-) rats than in TBI epileptic (TBI+) rats. During the Morris water maze probe trial, TBI rats took significantly longer to locate the platform (p< 0.0001), compared to sham rats indicating cognitive impairment while no significant difference was observed between TBI+ and TBI- rats. Logistic regression analysis of thalamus SUV and Morris water maze data differentiated between the TBI+ and TBI- animals (AUC 0.83).
Conclusions: After TBI, there was a differently elevated level of TSPO expression in TBI+ and TBI- rats as determined by PET imaging, suggesting a persistent but differential microglial activation phenotypes between the two groups. Imaging inflammation by these techniques could be a potential predictive biomarker for epilepsy and holds the promise of clinical translation.
Funding: Department of Defense, USA
Grant no- W81XWH-21-1-0927 (IA)
Translational Research