<scp>Translocator protein positron emission tomography</scp> as a biomarker for posttraumatic epilepsy and behavioral comorbidities following traumatic brain injury

Abstract Objective Traumatic brain injury (TBI) induces widespread and persistent neuroinflammation, which is increasingly recognized as a key contributor to chronic sequelae including posttraumatic epilepsy (PTE), cognitive deficits, and neuropsychiatric disturbances. However, reliable biomarkers for identifying individuals at risk for these long‐term outcomes remain limited. In this study, we evaluated in vivo positron emission tomography (PET) imaging of the 18‐kDa translocator protein (TSPO) as a predictive biomarker of epileptogenesis and neurobehavioral dysfunction in a rat model of moderate–severe TBI. Methods Adult rats received lateral fluid percussion injury ( n = 61) or sham surgery ( n = 14). TSPO PET was performed using [ 18 F]‐PBR06 at 1 and 4 weeks postinjury. Long‐term behavioral outcomes were assessed at 5–6 months post‐TBI, followed by continuous 4‐week video‐electroencephalographic monitoring during 7 th month to identify epileptic rats. Results TBI rats demonstrated robust and sustained increases in TSPO binding across multiple brain regions at both time points compared with sham animals ( p &lt; .001). At 4 weeks postinjury, however, TSPO binding in the cortex, hippocampus, and thalamus was significantly lower in rats that later developed epilepsy (PTE + ) than in those that did not (PTE − ; p &lt; .05), with receiver operating characteristic (ROC) analysis showing good predictive performance (area under the curve [AUC] = .76, p &lt; .01). Behavioral testing identified deficits in spatial learning, memory, and open‐field activity in TBI rats ( p &lt; .05). Data‐driven stratification identified behaviorally impaired (TBI‐BI + ) and unimpaired (TBI‐BI − ) subgroups, with cortical TSPO moderately distinguishing impaired animals (AUC ≈ .7). Among impaired rats, those with multidomain behavioral deficits ( n = 33) showed elevated thalamic TSPO compared to those with a single impairment ( p = .032), with ROC analysis confirming discrimination (AUC = .72, p = .018). Significance Our findings support TSPO PET imaging as a promising early biomarker for predicting PTE and neurobehavioral outcomes following TBI.