In a path breaking research, scientists have for the first time shown that chemotherapy may make patients susceptible to a syndrome of delayed degeneration in the central nervous system (CNS) called "chemobrain".
Their finding is based on a study on mice that focussed on a chemotherapeutic agent called 5-fluorouracil (5-FU), which is employed in the treatment of cancers of the colon, rectum, breast, stomach, pancreas, ovaries, and bladder.
During the study, Professor Mark Noble and his colleagues at the University of Rochester Stem Cell and Regenerative Medicine Institute and the Harvard Medical School, Boston discovered that short-term systematic administration of 5-FU to mice caused both acute CNS damage and a syndrome of progressively worsening delayed damage.
The damage was not self-repairing, and instead became worse over time.
The study also revealed that treatment with chemotherapy had delayed effects on the speed with which information is transferred from the ear to the brain.
Based on their observations, the researchers came to the conclusion that clinically relevant concentrations of 5-FU were toxic not only for dividing cells of the CNS, but also for the cells that produce the insulating myelin sheaths, non-dividing oligodendrocytes that are necessary for normal neuronal function.
The delayed damage the researchers measured was to the myelinated tracts of the CNS, and associated with extensive myelin pathology.
The research team says that their findings regarding the speed of ear-to-brain information transfer may offer a non-invasive means of analysing myelin damage associated with cancer treatment.
"Multiple clinical reports have identified neurotoxicity as a complication of treatment regimens in which chemotherapeutic agents such as 5-fluorouracil are components. As treatments with chemotherapeutic agents will clearly remain the standard of care for cancer patients for many years to come, the need to better understand such damage is great," says Noble.
Professor Noble adds: "These studies extend the field of stem cell medicine beyond the use of cell transplantation for tissue repair. It is our knowledge of stem cell biology that allows us to begin to understand some of the causes of this syndrome, as well as providing the means of preventing or repairing this damage."
The researchers claim that they are the first to show that delayed CNS damage can be induced by a single chemotherapeutic agent. They also claim to generate the first animal model of such damage.
The study has been reported in the open access Journal of Biology.