Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677, Japan.
F1000Res. 2020 Jan 20;9:29. doi: 10.12688/f1000research.21132.1. eCollection 2020.
Traumatic brain injury (TBI) in the form of diffuse axonal injury (DAI) is difficult to diagnose in the early phase of the injury. Early diagnosis of DAI may provide opportunity for developing treatment and management strategies. Tau protein has been demonstrated to increase in the early phase of TBI with high diagnostic accuracy in patients with DAI. We tested the biological plausibility of tau protein using a rat DAI model by evaluating the association between serum tau levels and the severity of brain injury. DAI was induced in animals using the Marmarou model. After a survival of 60 minutes, rats were anesthetized and sacrificed after obtaining blood samples (5ml) from the heart. Eighteen rats were employed in the present study and were randomly subjected to sham-operated control (n=4), mild DAI (n=7), and severe DAI (n=7). Of seven severe DAI rats, two rats that had focal injury caused by skull fracture were excluded in the measurement of tau protein level. The serum levels of tau protein in the rat DAI model were found to increase significantly and consistently according to the severity of the injury. Rats with DAI showed significantly higher serum levels of tau protein compared to sham rats; the severe DAI rats had higher levels of tau than moderate DAI and sham rats (sham vs. mild, =0.02; mild vs. severe, =0.02). In conclusion, serum tau protein levels may be useful as a biomarker for diagnosing and estimating the severity of DAI in the early phase.
创伤性脑损伤（TBI）以弥漫性轴索损伤（DAI）的形式存在，在损伤的早期阶段很难诊断。早期诊断 DAI 可能为制定治疗和管理策略提供机会。研究已经表明，TBI 早期tau 蛋白会增加，并且在 DAI 患者中具有较高的诊断准确性。我们通过评估血清 tau 水平与脑损伤严重程度之间的关系，使用大鼠 DAI 模型来测试 tau 蛋白的生物学合理性。通过使用 Marmarou 模型在动物中诱导 DAI。在 60 分钟的存活后，通过心脏抽取 5ml 血液样本后对动物进行麻醉和处死。本研究共纳入 18 只大鼠，随机分为假手术对照组（n=4）、轻度 DAI 组（n=7）和重度 DAI 组（n=7）。在 7 只重度 DAI 大鼠中，有 2 只大鼠由于颅骨骨折导致局灶性损伤，因此排除在 tau 蛋白水平测量之外。根据损伤的严重程度，大鼠 DAI 模型中的 tau 蛋白血清水平显著且一致地增加。与假手术大鼠相比，DAI 大鼠的血清 tau 蛋白水平显著升高；重度 DAI 大鼠的 tau 水平高于中度 DAI 和假手术大鼠（假手术 vs. 轻度，p=0.02；轻度 vs. 重度，p=0.02）。总之，血清 tau 蛋白水平可能作为诊断和评估 DAI 早期严重程度的生物标志物有用。
