Astrogliosis marker (11)C-SL25.1188 PET in traumatic brain injury with persistent symptoms

Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B (MAO-B) total distribution volume ((11)C-SL25.1188 V(T)), an index of MAO-B density, was measured in 29 TBI and 29 similarly aged healthy control cases with (11)C-SL25.1188 PET, prioritizing prefrontal cortex (PFC) and cortex proximal to cortical convexity. Correlations of PFC (11)C-SL25.1188 V(T) with psychomotor and processing speed; and serum blood measures implicated in astrogliosis were determined. (11)C-SL25.1188 V(T) was greater in TBI in PFC (P = 0.00064) and cortex (P = 0.00038). PFC (11)C-SL25.1188 V(T) inversely correlated with Comprehensive Trail Making Test psychomotor and processing speed (r = −0.48, P = 0.01). In participants scanned within 2 years of last TBI, PFC (11)C-SL25.1188 V(T) correlated with serum glial fibrillary acid protein (r = 0.51, P = 0.037) and total tau (r = 0.74, P = 0.001). Elevated (11)C-SL25.1188 V(T) argues strongly for astrogliosis and therapeutics modifying astrogliosis towards curative phenotypes should be tested in TBI with persistent symptoms. Given substantive effect size, astrogliosis PET markers should be applied to stratify cases and/or assess target engagement for putative therapeutics targeting astrogliosis.