Molecular imaging of neuroinflammation in patients after mild traumatic brain injury: a longitudinal 123 I-CLINDE single photon emission computed tomography study.

Abstract

Neuroinflammation has been proposedas part ofthe pathogenesis of post-concussionsymptoms (PCS), but the inflammatory response of the human brain to mildtraumatic brain injury (mTBI) remains unknown. We hypothesized that a neuroinflammatory responseis present in mTBI at 1-2weeks post-injury and persists in patients with PCS. We scanned 14 patients with mTBI without signs of structural damage at 1-2weeks and 3-4months post-injury and 22 healthy controlsonceusing the single photon emission computed tomography tracer 123 I-CLINDE, which visualizes translocator protein(TSPO), aprotein upregulated in active immune cells. PCS was defined as three or more persisting symptoms from theRivermead Post Concussion SymptomsQuestionnaireat 3monthspost-injury. Across brain regions, patients had significantly higher 123 I-CLINDE binding to TSPO than healthy controls, both at 1-2weeks after the injury in all patients (P=0.011) and at 3-4months in the seven patients with PCS (P=0.006) and in the six patients with good recovery (P=0.018). When the nine brain regions were tested separately and results were corrected for multiple comparisons, no individual region differed significantly, but all estimated parameters indicated increased 123 I-CLINDEbinding to TSPO,ranging from 2% to 19% in all patients at 1-2weeks, 13% to 27% in patients with PCS at 3-4months and -9% to 17% in patients with good recovery at 3-4months. Neuroinflammationwas presentinmTBI at1-2weeks post-injury and persisted at 3-4months post-injury with a tendency to be most pronounced in patients with PCS.