Department of Anaesthesia and Intensive Care, Fondazione IRCCS Ca Granda-Ospedale Maggiore Policlinico, Milan University, Milano 20100, Italy.
Brain. 2012 Apr;135(Pt 4):1268-80. doi: 10.1093/brain/awr286. Epub 2011 Nov 23.
Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. To test this hypothesis, 100 kDa cut-off microdialysis catheters were placed in 16 patients with severe traumatic brain injury at two neurological/neurosurgical intensive care units. Tau levels in the microdialysis samples were highest early and fell over time in all patients. Initial tau levels were >3-fold higher in patients with microdialysis catheters placed in pericontusional regions than in patients in whom catheters were placed in normal-appearing right frontal lobe tissue (P = 0.005). Tau levels and neurofilament light-chain levels were positively correlated (r = 0.6, P = 0.013). Neurofilament light-chain levels were also higher in patients with pericontusional catheters (P = 0.04). Interestingly, initial tau levels were inversely correlated with initial amyloid-β levels measured in the same samples (r = -0.87, P = 0.000023). This could be due to reduced synaptic activity in areas with substantial axonal injury, as amyloid-β release is closely coupled with synaptic activity. Importantly, high initial tau levels correlated with worse clinical outcomes, as assessed using the Glasgow Outcome Scale 6 months after injury (r = -0.6, P = 0.018). Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of patients will be required to assess the reproducibility of these findings and to determine whether this approach provides added value when combined with clinical and radiological information.
轴突损伤被认为是创伤性脑损伤后不良预后的主要决定因素。然而，在人类创伤性脑损伤患者中，很难在急性期评估轴突损伤的严重程度。我们假设，基于微透析的脑细胞外液中 tau 和神经丝轻链这两种低分子量轴突蛋白的测量可能对此有所帮助。为了验证这一假设，在两个神经科/神经外科重症监护病房，将 100 kDa 截止微透析导管放置在 16 例严重创伤性脑损伤患者中。所有患者的微透析样本中的 tau 水平在早期最高，并且随着时间的推移而下降。在将导管置于脑损伤区的患者中，初始 tau 水平比在将导管置于正常外观的右额叶组织的患者中高 3 倍以上（P=0.005）。tau 水平与神经丝轻链水平呈正相关（r=0.6，P=0.013）。在放置在脑损伤区的患者中，神经丝轻链水平也更高（P=0.04）。有趣的是，初始 tau 水平与在相同样本中测量的初始淀粉样蛋白-β水平呈负相关（r=-0.87，P=0.000023）。这可能是由于在有大量轴突损伤的区域中突触活动减少，因为淀粉样蛋白-β的释放与突触活动密切相关。重要的是，高初始 tau 水平与受伤后 6 个月使用格拉斯哥结局量表评估的较差临床结局相关（r=-0.6，P=0.018）。综上所述，我们的数据为轴突损伤可能与创伤性脑损伤后的长期损伤有关的假说提供了支持。基于微透析的脑细胞外空间 tau 水平的测量可能是一种在重症监护病房中急性评估轴突损伤严重程度的有用方法。需要更多的患者进行进一步研究，以评估这些发现的可重复性，并确定这种方法与临床和影像学信息结合使用是否具有附加价值。
