Study Reveals Culprits Behind “Chemo Brain” in Cancer Patients

A new study on mice has identified immune cells that keep the brain “clean” and contribute to inflammation as the culprits responsible for concentration and memory problems that sometimes follow a particular chemotherapy treatment. The research team showed that female mice given paclitaxel, a drug used to treat breast, ovarian, and other cancers, developed memory problems linked to inflammation in the brain. However, mice that received a placebo did not experience such cognitive impairment.

The team used a technique to delete immune cells called microglia from the brains of mice that received paclitaxel. The loss of those cells restored the chemo-treated animals’ memory and also reduced inflammation in their brains. The research was published recently in the journal Brain, Behavior, and Immunity.

The team intended to study only the effects of paclitaxel, often combined with one or more additional drugs in regimens designed to provide the most effective treatment for certain types of breast cancer. Pyter, the senior author and associate professor of psychiatry and behavioral health at Ohio State’s College of Medicine, is also studying how the gut microbiome may play a role in chemo brain.

The team predicts that inflammatory cells in the rest of the body, known as the periphery, are sending signals that activate microglia to become pro-inflammatory in the brain, hinting at three potential areas to target. The researchers found that both microglia and astrocytes, cells in the brain that have an immune role but also perform numerous functions to keep neurons healthy, were activated by chemotherapy in the hippocampus, the region of focus in this work.

According to Pyter, drugs similar to this experimental compound have been used in cancer patients receiving paclitaxel to target other types of immune cells, which suggests that temporarily clearing away microglia in humans may be feasible. She explains, “A better understanding of how chemotherapy affects the brain opens up research areas and interventions to improve the lives of our cancer patients.”

This study is a first step toward proposing potential interventions that could lessen the impact of chemotherapy on the body and brain. Chemotherapy agents work by killing cancer cells, but they also kill other dividing cells, and the immune system clean-up of resulting debris is thought to drive inflammation. Identifying chemotherapy side effects, cells, and pathways involved in animal studies is the first crucial step for therapeutic interventions with human patients.