Researchers also hypothesized that chemotherapy drugs known to cross the blood-brain barrier would be a bigger threat to brain cells than drugs that do not cross the blood-brain barrier. To test the hypothesis, they investigated the effects of routinely used doses of cyclophosphamide and fluorouracil, which do cross into the brain, against paclitaxel and doxorubicin, which do not.
Unexpectedly, all four drugs caused a significant breakdown in brain cell proliferation in the animal model. A statistical analysis of cell regeneration showed a 15.4 percent reduction in new brain cells following fluorouracil, a 30.5 percent reduction following cyclophosphamide, a 22.4 percent reduction following doxorubicin, and a 36 percent reduction following paclitaxel.
"It could be that all of the chemo drugs cross into the brain after all, or that they act via peripheral mechanisms, such as inflammation, that could open up the blood-brain barrier," Gross said.
"Neurogenesis can also be altered by stress, sleep deprivation and depression, all of which are common among cancer patients," added Janelsins. "More thorough studies are needed to understand the interplay of these factors and the long-term effects of chemotherapy on the brain."
Researchers conducted a second study of a single high dose of cyclophosphamide, a mainstay of adjuvant chemotherapy for breast cancer, because chemo-brain is a frequent complaint of people receiving this drug. The single high dose resulted in a 40.9 percent reduction in newly divided brain cells, the study said.
In previous studies the experimental growth hormone IGF-1 had demonstrated that it could generally promote new brain cell development within the central nervous system. Thus, investigators chose to test its effect in the animal model.
|Contact: Leslie Orr and Leslie White|
University of Rochester Medical Center