Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy.
Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy.
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DOI：
10.3389/fimmu.2020.626687
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发表时间：
2020
影响因子：
7.3
通讯作者：
Meregalli C
中科院分区：
文献类型：
--
作者：
Fumagalli G;Monza L;Cavaletti G;Rigolio R;Meregalli C
周围神经病以神经损伤和轴突丧失为特征，可分为遗传性和后天性两种。获得性周围神经病变与多种原因有关，包括毒性物质暴露，其中抗肿瘤化合物负责所谓的化疗诱导周围神经病变（CIPN）。一些临床特征与抗癌药物的使用有关，这些药物通过影响周围神经系统的不同机制和结构来发挥作用：轴突（轴突病）或背根神经节（DRG）神经元细胞体（神经病/神经节病）。此外，抗肿瘤治疗可能会影响血脑屏障的完整性，导致严重和持久的认知障碍。CIPN可能影响患者的生活质量，导致改变或停止抗癌治疗。尽管损伤的机制尚不完全清楚，但已经提出了几种假设，其中神经炎症现在正在出现与CIPN病理生理学相关。在这篇综述中，我们考虑了几个CIPN临床前研究中神经免疫相互作用的不同方面，这些研究表明化疗药物和神经毒性之间存在重要联系。神经炎症过程的特征可能因药物类型（铂衍生物、紫杉烷、长春花生物碱和蛋白酶体抑制剂）而异。特别是，最近的研究表明，免疫反应（先天和适应性）和介质（细胞因子和趋化因子）的刺激和分泌可能与疼痛症状有关，而卫星细胞和雪旺细胞等神经胶质细胞可能分别有助于DRG和轴突神经炎症过程的维持。此外，神经炎症成分也显示在脊髓中，小胶质细胞和星形胶质细胞在CIPN的发展中起重要作用。综上所述，更好地理解这些方面将允许制定可能的战略，以改善CIPN的管理。
Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) neurons cell body (neuronopathy/ganglionopathy). In addition, antineoplastic treatments may affect the blood brain barrier integrity, leading to cognitive impairment that may be severe and long-lasting. CIPN may affect patient quality of life leading to modification or discontinuation of the anticancer therapy. Although the mechanisms of the damage are not completely understood, several hypotheses have been proposed, among which neuroinflammation is now emerging to be relevant in CIPN pathophysiology. In this review, we consider different aspects of neuro-immune interactions in several CIPN preclinical studies which suggest a critical connection between chemotherapeutic agents and neurotoxicity. The features of the neuroinflammatory processes may be different depending on the type of drug (platinum derivatives, taxanes, vinca alkaloids and proteasome inhibitors). In particular, recent studies have demonstrated an involvement of the immune response (both innate and adaptive) and the stimulation and secretion of mediators (cytokines and chemokines) that may be responsible for the painful symptoms, whereas glial cells such as satellite and Schwann cells might contribute to the maintenance of the neuroinflammatory process in DRG and axons respectively. Moreover, neuroinflammatory components have also been shown in the spinal cord with microglia and astrocytes playing an important role in CIPN development. Taking together, better understanding of these aspects would permit the development of possible strategies in order to improve the management of CIPN.
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