Skurlova M, Holubova K, Kleteckova L, Kozak T, Kubova H, Horacek J, Vales K
Department of Experimental Psychopharmacology, National Institute of Mental Health, Klecany, Czech Republic.
Department of Developmental Epileptology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Med Res Rev. 2024 Jan;44(1):5-22. doi: 10.1002/med.21977. Epub 2023 Jun 2.
Cancer treatment brings about a phenomenon not fully clarified yet, termed chemobrain. Its strong negative impact on patients' well-being makes it a trending topic in current research, interconnecting many disciplines from clinical oncology to neuroscience. Clinical and animal studies have often reported elevated concentrations of proinflammatory cytokines in various types of blood cancers. This inflammatory burst could be the background for chemotherapy-induced cognitive deficit in patients with blood cancers. Cancer environment is a dynamic interacting system. The review puts into close relationship the inflammatory dysbalance and oxidative/nitrosative stress with disruption of the blood-brain barrier (BBB). The BBB breakdown leads to neuroinflammation, followed by neurotoxicity and neurodegeneration. High levels of intracellular reactive oxygen species (ROS) induce the progression of cancer resulting in increased mutagenesis, conversion of protooncogenes to oncogenes, and inactivation of tumor suppression genes to trigger cancer cell growth. These cell alterations may change brain functionality, as well as morphology. Multidrug chemotherapy is not without consequences to healthy tissue and could even be toxic. Specific treatment impacts brain function and morphology, functions of the immune system, and metabolism in a unique mixture. In general, a chemo-drug's effects on cognition in cancer are not direct and/or in-direct, usually a combination of effects is more probable. Last but not least, chemotherapy strongly impacts the immune system and could contribute to BBB disruption. This review points out inflammation as a possible mechanism of brain damage during blood cancers and discusses chemotherapy-induced cognitive impairment.
癌症治疗引发了一种尚未完全阐明的现象，称为化疗脑。它对患者健康产生的强烈负面影响使其成为当前研究中的一个热门话题，将从临床肿瘤学到神经科学的许多学科联系在一起。临床和动物研究经常报告各种类型的血癌中促炎细胞因子浓度升高。这种炎症爆发可能是血癌患者化疗引起的认知缺陷的背景。癌症环境是一个动态的相互作用系统。这篇综述将炎症失衡、氧化/亚硝化应激与血脑屏障（BBB）破坏紧密联系起来。血脑屏障的破坏会导致神经炎症，进而引发神经毒性和神经退行性变。高水平的细胞内活性氧（ROS）会诱导癌症进展，导致诱变增加、原癌基因转化为癌基因以及肿瘤抑制基因失活，从而触发癌细胞生长。这些细胞改变可能会改变大脑功能以及形态。多药化疗对健康组织并非没有影响，甚至可能具有毒性。特定的治疗会以独特的组合方式影响脑功能和形态、免疫系统功能以及新陈代谢。一般来说，化疗药物对癌症患者认知的影响并非直接和/或间接的，通常更可能是多种影响的组合。最后但同样重要的是，化疗会强烈影响免疫系统，并可能导致血脑屏障破坏。这篇综述指出炎症是血癌期间脑损伤的一种可能机制，并讨论了化疗引起的认知障碍。
