Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

Overview

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood, but inflammation is potentially an important but still undervalued factor. Here we present a first-in-human prospective study using translocator protein 18 kDa (TSPO) radioligand (F18-DPA714) for PET imaging, to allow in vivo neuroimmune activation quantification on patients with coma (n = 17) following either anoxia or traumatic brain injuries and compare with age and sex-matched controls. Our findings yield novel evidence that an early inflammatory component that is predominantly located within key cortical and subcortical brain structures which are putatively implicated in consciousness emergence and maintain after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and the specifically distributed PET-measurable neuroinflammation within the brain mesocircuit were associated with patient's potential of recovery. We suggest that our results can be developed for use both as a new neuroprognostication tool and as promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.