Astrogliosis marker 11C-SL2511.88 PET in traumatic brain injury with persistent symptoms.

Abstract

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 total distribution volume ([11C]SL25.1188 VT), an index of MAO-B density, was measured in 29 TBI and 29 similarly aged healthy control cases with [11C]SL25.1188 PET, prioritizing prefrontal cortex (PFC) and cortex proximal to cortical convexity. Correlations of PFC [11C]SL25.1188 VT with psychomotor and processing speed; and serum blood measures implicated in astrogliosis were determined. [11C]SL25.1188 VT was greater in TBI in PFC (P=0.00064) and cortex (P=0.00038). PFC [11C]SL25.1188 VT inversely correlated with Comprehensive Trail Making Test psychomotor and processing speed (r=-0.48, P=0.01). In participants scanned within two years of last TBI, PFC [11C]SL25.1188 VT correlated with serum glial fibrillary acid protein (r=0.51, P=0.037) and total tau (r=0.74, P=0.001). Elevated [11C]SL25.1188 VT 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.