Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI.
Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI.
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DOI：
10.3390/ijms232315208
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发表时间：
2022-12-02
影响因子：
5.6
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中科院分区：
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血浆神经丝轻链(NF-L)水平被评估为创伤性脑损伤的诊断生物标记物和躯体运动恢复、认知功能减退和癫痫发生的预后生物标记物。采用大鼠一侧液压冲击伤(26只，13只伴癫痫，13只不伴癫痫)或假手术(8只)制作重型颅脑损伤模型。在6个月的随访中，大鼠在6个月期间接受磁共振成像(MRI)(D2、D7和D21)、综合神经评分(D2、D6和D14)、Morris水迷宫(D35-D39)和长达1个月的视频脑电检查，以检测6个月期间的无缘性癫痫发作。用单分子测定法测定基础状态(即幼稚动物)和脑损伤或假手术后D2、D9和D178的血浆核因子-L水平。与伤前比较，伤后第2天(5072.0±2007.0 pg/mL)、第9天(930.3±306.4 pg/mL)和第3天(32.2±8.9pg/mL)分别升高483倍、89倍和3倍(10.5±2.6pg/mL；均P<0.001)。血浆中核因子-L水平在检测的各个时间点(曲线下面积(AUC1.0，p<；0.001)和假手术对照组(AUC1.0，p<；0.001)将脑创伤大鼠与幼稚动物区分开来。D2时血浆中核因子-L的升高与躯体运动功能损害程度(ρ=−0.480)和核磁共振检查皮质损害程度(ρ=0.401，p<；0.05)相关。伤后6个月血浆核因子-L水平升高与伤后6个月组织学切片中皮质损伤程度呈正相关(ρ=0.437；ρ=0.393，P<0.05)。然而，血浆中的核因子-L水平并不能预测躯体运动恢复、认知功能减退或癫痫的发生(p>；0.05)。血浆核因子-L水平是急性颅脑损伤的无创性翻译诊断标志物，是创伤后躯体运动功能障碍和长期结构性脑损伤的预后标志物。
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.
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