Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research, Hajipur, Bihar, India.
Adv Cancer Res. 2022;155:29-76. doi: 10.1016/bs.acr.2022.04.001. Epub 2022 May 11.
Chemo-brain refers to the thinking and memory problems that occur in cancer patients during and after chemotherapy. It is also known as cognitive dysfunction or chemo-fog. Risk factors include brain malignancies, either primary or metastatic, radiotherapy and chemotherapy, either systemic or brain targeted. There are various mechanisms by which chemo-brain occurs in patients post-chemotherapy, including inflammation of neurons, stress due to free radical generation, and alterations in normal neuronal cell process due to biochemical changes. While chemotherapy drugs that are non-brain targeted, usually fail to cross the blood-brain barrier (BBB), this is not the case for inflammatory cytokines that are released, which easily cross the BBB. These inflammatory neurotoxic agents may represent the primary mediators of chemobrain and include the pro-inflammatory cytokines such as interleukins 1 and 6 and tumor necrosis factor. The pronounced rise in oxidative stress due to continuous chemotherapy also leads to a reduction in neurogenesis and gliogenesis, loss of spine and dendritic cells, and a reduction in neurotransmitter release. Based on recent research, potential agents to prevent and treat chemo brain have been identified, which include Lithium, Fluoxetine, Metformin, Rolipram, Astaxanthin, and microglial inhibitors. However, more defined animal models for cognitive dysfunction are required to study in detail the mechanisms involved in chemo-brain; furthermore, well-defined clinical trials are required to identify drug targets and their therapeutic significance. With these focused approaches, the future for improved therapies is promising.
化疗脑是指癌症患者在化疗期间和化疗后出现的思维和记忆问题。它也被称为认知功能障碍或化疗雾。风险因素包括脑恶性肿瘤，无论是原发性还是转移性的，放疗和化疗，无论是全身还是脑部靶向的。化疗后患者发生化疗脑的机制有多种，包括神经元炎症、自由基生成引起的应激以及生化变化导致正常神经元细胞过程改变。虽然非脑部靶向的化疗药物通常无法穿过血脑屏障 (BBB)，但释放的炎症细胞因子则不然，它们很容易穿过 BBB。这些炎症性神经毒性物质可能是化疗脑的主要介质，包括促炎细胞因子如白细胞介素 1 和 6 以及肿瘤坏死因子。由于持续化疗导致氧化应激显著增加，也会导致神经发生和神经胶质发生减少、棘突和树突细胞丢失以及神经递质释放减少。基于最近的研究，已经确定了一些预防和治疗化疗脑的潜在药物，包括锂、氟西汀、二甲双胍、罗利普兰、虾青素和小胶质细胞抑制剂。然而，需要更明确的认知功能障碍动物模型来详细研究化疗脑涉及的机制；此外，还需要明确的临床试验来确定药物靶点及其治疗意义。通过这些有针对性的方法，改善治疗的未来前景广阔。
