Heiskanen Mette, Banuelos Ivette, Manninen Eppu, Andrade Pedro, Hämäläinen Elina, Puhakka Noora, Pitkänen Asla
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Epilepsia. 2024 Dec;65(12):3703-3716. doi: 10.1111/epi.18149. Epub 2024 Oct 14.
This study was undertaken to test whether the postinjury plasma concentration of phosphorylated neurofilament heavy chain (pNF-H), a marker of axonal injury, is a prognostic biomarker for the development of posttraumatic epilepsy.
Tail vein plasma was sampled 48 h after traumatic brain injury (TBI) from 143 rats (10 naïve, 21 controls, 112 with lateral fluid percussion injury) to quantify pNF-H by enzyme-linked immunosorbent assay. During the 6th postinjury month, rats underwent 30 days of continuous video-electroencephalographic monitoring to detect unprovoked seizures and evaluate epilepsy severity. Somatomotor (composite neuroscore) and spatial memory (Morris water maze) testing and quantitative T magnetic resonance imaging were performed to assess comorbidities and lesion severity.
Of the 112 TBI rats, 25% (28/112) developed epilepsy (TBI+) and 75% (84/112) did not (TBI-). Plasma pNF-H concentrations were higher in TBI+ rats than in TBI- rats (p < .05). Receiver operating characteristic curve analysis indicated that plasma pNF-H concentration distinguished TBI+ rats from TBI- rats (area under the curve [AUC] = .647, p < .05). Differentiation was stronger when comparing TBI+ rats exhibiting severe epilepsy (≥3 seizures/month) with all other TBI rats (AUC = .732, p < .01). Plasma pNF-H concentration on day 2 (D2) distinguished TBI+ rats with seizure clusters from other TBI rats (AUC = .732, p < .05). Higher plasma pNF-H concentration on D2 after TBI correlated with lower neuroscores on D2 (p < .001), D6 (p < .001), and D14 (p < .01). Higher pNF-H concentration on D2 correlated with greater T signal abnormality volume on D2 (p < .001) and D7 (p < .01) and larger cortical lesion area on D182 (p < .01). Plasma pNF-H concentration on D2 did not correlate with Morris water maze performance on D37-D39.
Plasma pNF-H is a promising clinically translatable prognostic biomarker for the development of posttraumatic epilepsy with frequent seizures or seizure clusters.
本研究旨在测试轴突损伤标志物磷酸化神经丝重链（pNF-H）伤后血浆浓度是否为创伤后癫痫发生的预后生物标志物。
对143只大鼠（10只未受伤、21只对照、112只接受侧方流体冲击伤）在创伤性脑损伤（TBI）后48小时采集尾静脉血浆，通过酶联免疫吸附测定法对pNF-H进行定量。在伤后第6个月期间，大鼠接受30天的连续视频脑电图监测，以检测无诱因癫痫发作并评估癫痫严重程度。进行躯体运动（综合神经评分）和空间记忆（莫里斯水迷宫）测试以及定量T磁共振成像，以评估合并症和损伤严重程度。
在112只TBI大鼠中，25%（28/112）发生癫痫（TBI+），75%（84/112）未发生癫痫（TBI-）。TBI+大鼠的血浆pNF-H浓度高于TBI-大鼠（p <.05）。受试者工作特征曲线分析表明，血浆pNF-H浓度可区分TBI+大鼠和TBI-大鼠（曲线下面积[AUC]=.647，p <.05）。将表现为严重癫痫（≥3次发作/月）的TBI+大鼠与所有其他TBI大鼠进行比较时，区分能力更强（AUC =.732，p <.01）。伤后第2天（D2）的血浆pNF-H浓度可区分有癫痫发作簇集的TBI+大鼠与其他TBI大鼠（AUC =.732，p <.05）。TBI后D2时较高的血浆pNF-H浓度与D2（p <.001）、D6（p <.001）和D14（p <.01）时较低的神经评分相关。D2时较高的pNF-H浓度与D2（p <.001）和D7（p <.01）时更大的T信号异常体积以及D182时更大的皮质损伤面积相关（p <.01）。D2时的血浆pNF-H浓度与D37 - D39时的莫里斯水迷宫表现无关。
血浆pNF-H是创伤后癫痫频繁发作或发作簇集发生的一种有前景的、可临床转化的预后生物标志物。
