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.

中文翻译：

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神经免疫激活与缺氧和创伤性昏迷的神经系统结果相关

人们对大脑连接体严重破坏导致昏迷的病理生理基础知之甚少，但炎症可能是一个重要但仍被低估的因素。在这里，我们提出了一项首次人体前瞻性研究，使用易位蛋白 18 kDa (TSPO) 放射性配体 (F18-DPA714) 进行 PET 成像，以对缺氧或创伤后昏迷患者 (n = 17) 进行体内神经免疫激活定量脑损伤并与年龄和性别匹配的对照进行比较。我们的研究结果提供了新的证据，表明早期炎症成分主要位于关键的皮质和皮质下脑结构内，这些结构被认为与严重脑损伤后意识的出现和维持有关（即中脑回路和额顶叶网络）。我们观察到，昏迷的创伤性和缺氧患者在强度和空间分布方面都具有不同的神经免疫激活特征。最后，我们证明大脑中间回路内 PET 可测量的神经炎症的总量和具体分布都与患者的康复潜力相关。我们建议，我们的结果可以开发用作新的神经预测工具和有前途的生物识别技术，以指导未来在严重脑损伤后早期针对神经胶质活动的临床试验。