Chemotherapy's Damage To The Brain Detailed is the title of an article in ScienceDaily.

"A commonly used chemotherapy drug causes healthy brain cells to die off long after treatment has ended and may be one of the underlying biological causes of the cognitive side effects -- or "chemo brain" -- that many cancer patients experience."

Implications:

• The study provides convincing evidence about neurological damage from infusion of 5-fluorouracil and helps to explain the delayed symptoms patients frequently report.
• Patients then conclude that their current medications (e.g., Tamoxifen, Arimidex) are responsible for their difficulties, and physicians often conclude that the patients’ response is due to the stress of treatment and not the treatment itself.

More information about the study

Mark Noble and a research team from the University of Rochester Medical Center (URMC) and Harvard Medical School uncovered evidence that is difficult to dispute:

the chemotherapy drug 5-fluorouracil (5-FU) is"  associated with a"  "progressing collapse" of populations of stem cells and their progeny in the central nervous system (CNS).

The findings about the destruction of stem cells has high importance:"  since stem cells have the capability to evolve into a wide range of cells and to regenerate," the destruction of these cells in the brain can have long-lasting, and potentially permanent, consequences.

"This study is the first model of a delayed degeneration syndrome that involves a global disruption of the myelin-forming cells that are essential for normal neuronal function," said Mark Noble, Ph.D., who serves as director of the University of Rochester Stem Cell and Regenerative Medicine Institute and was senior author of the study. "Because of our growing knowledge of stem cells and their biology, we can now begin to understand and define the molecular mechanisms behind the cognitive difficulties that linger and worsen in a significant number of cancer patients."

More information
University of Rochester Medical Center (2008, April 22). Chemotherapy's Damage To The Brain Detailed. ScienceDaily. Retrieved May 14, 2009.

Abstract of the Journal article documenting the study and the researchers' conclusions

J Biol. 2008;7(4):12. Epub 2008 Apr 22.Click here to read Click here to read Links
Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system.
Han R, Yang YM, Dietrich J, Luebke A, Mayer-Pröschel M, Noble M.

Department of Biomedical Genetics and University of Rochester Stem Cell and Regenerative Medicine Institute, University of Rochester Medical Center, Elmwood Avenue, Rochester, NY 14642, USA. This e-mail address is being protected from spambots. You need JavaScript enabled to view it

BACKGROUND : Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem.

RESULTS : We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent) were toxic for both central nervous system (CNS) progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology.

Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment.

CONCLUSIONS : Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.