Neurofilament light chain: a specific serum biomarker of axonal damage severity in rat models of Chemotherapy-Induced Peripheral Neurotoxicity
Neurofilament light chain: a specific serum biomarker of axonal damage severity in rat models of Chemotherapy-Induced Peripheral Neurotoxicity
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DOI：
10.1007/s00204-020-02755-w
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发表时间：
2020-04-24
影响因子：
6.1
通讯作者：
Marmiroli, Paola
中科院分区：
文献类型：
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作者：
Meregalli, Cristina;Fumagalli, Giulia;Marmiroli, Paola
化疗诱导的周围神经毒性（CIPN）是一种严重且持久的副作用，可严重影响患者的生活质量。它是一种感觉和长度依赖性神经病，主要影响大的有髓纤维。容易和可靠地监测患者中的CIPN仍然是未满足的临床需求。由于越来越多的临床证据支持神经丝轻链（NfL）作为轴突损伤的生物标志物的潜在用途，在这项研究中，我们测量了长期接受顺铂（CDDP）和紫杉醇（PTX）治疗的动物的血清NfL水平，这两种药物具有不同的神经元靶点。Wistar大鼠用CDDP（2 mg/kg i. p.，每周两次，持续4周）或PTX（10 mg/kg i. v.，每周一次，持续4周）处理。使用单分子阵列（Simoa）技术获得重复的血清NfL定量。通过神经生理学、形态学评估和表皮内神经纤维密度定量评价周围神经毒性的发生和进展。我们的研究结果表明，血清NfL测量与轴突损伤的严重程度。事实上，两种治疗均诱导血清NfL增加，但与CDDP治疗的大鼠相比，PTX治疗的动物受轻度神经毒性影响的水平更高。值得注意的是，NfL水平增加的时间也与轴突结构的形态和功能改变的严重程度相关。因此，NfL可能是轴突损伤的有用生物标志物，以跟踪轴突变性的发生和严重程度，并可能限制严重PNS疾病的发生。
Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a severe and long-lasting side effect of anticancer therapy, which can severely impair patients' quality of life. It is a sensory and length-dependent neuropathy, which predominantly affects large myelinated fibers. Easy and reliable monitoring of CIPN in patients is still an unmet clinical need. Since increasing clinical evidence supports the potential use of neurofilament light chain (NfL) as a biomarker of axonal injury, in this study we measured serum NfL levels in animals chronically treated with cisplatin (CDDP) and paclitaxel (PTX), two antineoplastic drugs with different neuronal targets. Wistar rats were treated with CDDP (2 mg/kg i.p. twice/week for 4 weeks) or PTX (10 mg/kg i.v. once/week for 4 weeks). Repeated serum NfL quantification was obtained using the Single Molecule Array (Simoa) technology. The onset and progression of peripheral neurotoxicity were evaluated through neurophysiology, morphological assessments and intraepidermal nerve fibers density quantification. Our results showed that serum NfL measurements correlated with the severity of axonal damage. In fact, both treatments induced serum NfL increase, but higher levels were evidenced in PTX-treated animals, compared with CDDP-treated rats, affected by a milder neurotoxicity. Notably, also the timing of the NfL level increase was associated with the severity of morphological and functional alterations of axonal structure. Therefore, NfL could be a useful biomarker for axonal damage in order to follow the onset and severity of axonal degeneration and possibly limit the occurrence of serious PNS disease.