eISSN: 2081-2833
ISSN: 2081-0016
Medycyna Paliatywna/Palliative Medicine
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vol. 14
Review paper

Mechanisms of chemotherapy-related cognitive impairment

Aleksandra Janota
Katarzyna Kołodziejczyk
Paulina Piechowicz
Piotr Dunaj
Tomasz Dzierżanowski

Pracownia Medycyny Paliatywnej, Zakład Medycyny Społecznej i Zdrowia Publicznego, Warszawski Uniwersytet Medyczny, Warszawa, Polska
Medycyna Paliatywna 2022; 14(3): 132–141
Online publish date: 2023/03/20
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Chemotherapy, an effective means in the fight against cancer, damages healthy tissues. More and more attention is being paid to chemobrain, which describes broadly defined cognitive disorders that manifest after anticancer treatment, with a particular focus on chemotherapy. There are numerous potential mechanisms of damage to the central nervous system, varying between distinct groups of chemotherapeutics. During treatment, there is an increased release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, both locally, mediated by activated microglia cells, and those peripherally produced that penetrate the blood-brain barrier. It leads to a local inflammatory response that disrupts neurogenesis and neuroplasticity within the hippocampus. Pro-inflammatory cytokines also increase oxidative stress in cells, inducing the production of free radicals that damage the mitochondrial membrane, causing mitochondrial dysfunction. This further enhances oxidative stress, considered one of the most important causal factors of chemobrain. The proapoptotic cascade is also activated, resulting in a picture of reduced hippocampal volume. For some drugs, mechanisms of direct neurotoxicity or disruption of cell division have also been postulated. In this article, we present the state of knowledge on the toxic effects on the central nervous system of representatives of each of the most commonly used groups of chemotherapeutics in clinical practice.

chemobrain, chemotherapy, cognitive impairment, chemotherapy-related cognitive impairment, CRCI

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