Greater Monoamine Oxidase B Distribution Volume In The Prefrontal Cortex In Traumatic Brain Injury with Persistent Symptoms: An [¹¹C]SL25.1188 Positron Emission Tomography Study

Objectives: Traumatic brain injury (TBI) has a lifetime prevalence of more than 10%, and a third of cases have long term symptoms, making TBI the most important cause of disability from neurological disease. There are no established pharmacological treatments for long term symptoms and a key barrier is a lack of targetable processes in community based samples of human TBI, which are of mild to moderate severity representing 90% of TBI cases. Gliosis (proliferation and activation of glial cells) occurs in chronic traumatic encephalopathy, but it is unknown whether gliosis occurs in the more common TBI of mild to moderate severity. Astroglial activation (activation and proliferation of astrocytes) is correlated with monoamine oxidase B (MAO-B) level in neuropsychiatric disease and may be applied as a marker of gliosis. [11C]SL25.1188 positron emission tomography (PET) may be applied to measure MAO-B total distribution volume (MAO-B V_T), an index of MAO-B density. It is hypothesized that MAO-B V_T is elevated in the prefrontal cortex (PFC) as well as in other cortex regions. Cortex regions are close to the skull and receive high levels of deformation stress in TBI models of direct and contra-coup injury, and the prefrontal cortex additionally plays an important role in cognitive functions often affected by TBI.

Methods: Seventeen healthy and 23 TBI cases with persistent symptoms were recruited from the community in Toronto, Canada. [11C]SL25.1188 PET was applied to measure MAO-B V_T, prioritizing the prefrontal cortex then other cortical regions, although a number of cortical and subcortical grey matter regions were also assessed. TBI cases had persistent symptoms since their last injury and no history of smoking, substance abuse, or psychotic illness.

Results: Patients with TBI had significantly greater MAO-B V_T in the PFC (18.7%, F1,38=10.76, P=0.002) and throughout the cortical regions (15.3%, F1,38=9.31; P=0.004). The effect sizes (Cohen’s d) were robust in the cortical regions, ranged from 0.97 and 1.24.

Conclusions: MAO-B V_T was highly elevated in the TBI group with an effect size of ~1.1 across cortical regions. This is strongly supportive of astrogliosis in community sampled TBI with persistent symptoms. This effect size is particularly notable, arguably being the largest among brain markers comparing mild to moderate severity TBI to controls.[11C]SL25.1188 PET shows intriguing promise for stratifying TBI cases with gliosis and monitoring treatments of TBI to reduce gliosis.