A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Institute of Clinical Medicine/Neurology, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Int J Mol Sci. 2022 Dec 2;23(23):15208. doi: 10.3390/ijms232315208.
Plasma neurofilament light chain (NF-L) levels were assessed as a diagnostic biomarker for traumatic brain injury (TBI) and as a prognostic biomarker for somatomotor recovery, cognitive decline, and epileptogenesis. Rats with severe TBI induced by lateral fluid-percussion injury (n = 26, 13 with and 13 without epilepsy) or sham-operation (n = 8) were studied. During a 6-month follow-up, rats underwent magnetic resonance imaging (MRI) (day (D) 2, D7, and D21), composite neuroscore (D2, D6, and D14), Morris-water maze (D35−D39), and a 1-month-long video-electroencephalogram to detect unprovoked seizures during the 6th month. Plasma NF-L levels were assessed using a single-molecule assay at baseline (i.e., naïve animals) and on D2, D9, and D178 after TBI or a sham operation. Plasma NF-L levels were 483-fold higher on D2 (5072.0 ± 2007.0 pg/mL), 89-fold higher on D9 (930.3 ± 306.4 pg/mL), and 3-fold higher on D176 32.2 ± 8.9 pg/mL after TBI compared with baseline (10.5 ± 2.6 pg/mL; all p < 0.001). Plasma NF-L levels distinguished TBI rats from naïve animals at all time-points examined (area under the curve [AUC] 1.0, p < 0.001), and from sham-operated controls on D2 (AUC 1.0, p < 0.001). Plasma NF-L increases on D2 were associated with somatomotor impairment severity (ρ = −0.480, p < 0.05) and the cortical lesion extent in MRI (ρ = 0.401, p < 0.05). Plasma NF-L increases on D2 or D9 were associated with the cortical lesion extent in histologic sections at 6 months post-injury (ρ = 0.437 for D2; ρ = 0.393 for D9, p < 0.05). Plasma NF-L levels, however, did not predict somatomotor recovery, cognitive decline, or epileptogenesis (p > 0.05). Plasma NF-L levels represent a promising noninvasive translational diagnostic biomarker for acute TBI and a prognostic biomarker for post-injury somatomotor impairment and long-term structural brain damage.
血浆神经丝轻链（NF-L）水平被评估为创伤性脑损伤（TBI）的诊断生物标志物，以及运动恢复、认知下降和癫痫发生的预后生物标志物。通过侧方液压冲击伤（n = 26，13 例伴癫痫和 13 例不伴癫痫）或假手术（n = 8）诱导严重 TBI 的大鼠进行了研究。在 6 个月的随访期间，大鼠接受了磁共振成像（MRI）（第 2 天（D2）、第 7 天和第 21 天）、综合神经评分（D2、D6 和 D14）、Morris 水迷宫（D35-D39）和 1 个月的视频脑电图以在第 6 个月检测自发性癫痫。在 TBI 或假手术后的基础上（即，未处理的动物）以及 D2、D9 和 D178 时使用单分子测定法评估血浆 NF-L 水平。与基线（10.5 ± 2.6 pg/mL）相比，TBI 后 D2（5072.0 ± 2007.0 pg/mL）时血浆 NF-L 水平高 483 倍，D9（930.3 ± 306.4 pg/mL）时高 89 倍，D176 32.2 ± 8.9 pg/mL 时高 3 倍（所有 p < 0.001）。血浆 NF-L 水平在所有检查时间点均能区分 TBI 大鼠与未处理的动物（曲线下面积 [AUC] 1.0，p < 0.001），并在 D2 时区分与假手术对照组（AUC 1.0，p < 0.001）。D2 时的血浆 NF-L 增加与运动障碍严重程度（ρ = −0.480，p < 0.05）和 MRI 中的皮质损伤程度（ρ = 0.401，p < 0.05）相关。D2 或 D9 时的血浆 NF-L 增加与伤后 6 个月的组织学切片中的皮质损伤程度相关（D2 时 ρ = 0.437；D9 时 ρ = 0.393，p < 0.05）。然而，血浆 NF-L 水平不能预测运动恢复、认知下降或癫痫发生（p > 0.05）。血浆 NF-L 水平代表急性 TBI 的有前途的非侵入性转化诊断生物标志物，以及运动障碍和长期结构脑损伤的预后生物标志物。
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