Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104.
Independent Researcher, Kengeri, Bangalore, Karnataka, India, 560060.
Psychopharmacology (Berl). 2021 Nov;238(11):3025-3053. doi: 10.1007/s00213-021-05977-7. Epub 2021 Oct 13.
Chemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person's day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment hypotheses and strategies.
A methodical evaluation of scientific literature is required to understand cognitive changes associated with the use of chemotherapeutic agents in different preclinical studies. This review mainly emphasizes animal models developed with various chemotherapeutic agents individually and in combination, with their proposed mechanisms contributing to the cognitive dysfunction. This review also points toward the analysis of chemobrain in healthy animals to understand the mechanism of interventions in absence of tumor and in tumor-bearing animals to mimic human cancer conditions to screen potential drug candidates against chemobrain.
Substantial memory deficit as a result of commonly used chemotherapeutic agents was evidenced in healthy and tumor-bearing animals. Spatial and episodic cognitive impairments, alterations in neurotrophins, oxidative and inflammatory markers, and changes in long-term potentiation were commonly observed changes in different animal models irrespective of the chemotherapeutic agent.
Dyscognition exists as one of the serious side effects of cancer chemotherapy. Due to differing mechanisms of chemotherapeutic agents with differing tendencies to alter behavioral and biochemical parameters, chemotherapy may present a significant risk in resulting memory impairments in healthy as well as tumor-bearing animals.
化疗引起的认知障碍（CICI）、化疗脑和化疗雾是癌症患者/幸存者在化疗药物影响下出现精神功能障碍的常用术语。CICI 表现为短期/长期记忆问题和精神处理延迟，干扰人的日常活动。了解 CICI 机制有助于开发治疗干预措施，可能减轻疾病状况。动物模型有助于进行关键评估，以阐明潜在机制，并成为验证不同治疗假设和策略的重要组成部分。
需要对科学文献进行系统评估，以了解与不同临床前研究中使用化疗药物相关的认知变化。本综述主要强调了使用各种化疗药物单独和联合开发的动物模型，以及它们对认知功能障碍的潜在机制。本综述还指出了在健康动物中分析化疗脑的必要性，以了解干预措施的机制，即在没有肿瘤的情况下，以及在荷瘤动物中模拟人类癌症状况，以筛选针对化疗脑的潜在药物候选物。
在健康和荷瘤动物中，常用化疗药物导致了明显的记忆缺陷。空间和情景认知障碍、神经营养因子、氧化和炎症标志物的改变以及长时程增强的变化，是不同动物模型中常见的变化，而与化疗药物无关。
认知障碍是癌症化疗的严重副作用之一。由于化疗药物的机制不同，改变行为和生化参数的趋势也不同，因此化疗可能会对健康和荷瘤动物的记忆损伤产生重大风险。
