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Summary: New research reveals that chemotherapy can cause “chemo brain” by damaging the brain’s lymphatic system, the network responsible for removing waste and supporting immune function. Using mouse models and human-engineered tissues, scientists found that common drugs such as docetaxel shrink lymphatic vessels and impair drainage, leading to memory deficits and cognitive decline.
The findings suggest that reduced lymph flow could be the cause of the mental confusion experienced by many cancer survivors, particularly women. Researchers now aim to explore therapies that restore brain lymphatic health without compromising cancer treatment.
Key facts:
Lymphatic link: Chemotherapy drugs, especially docetaxel, shrink the brain’s lymphatic vessels and reduce their drainage capacity. Effects on memory: Mice treated with these drugs showed memory impairment, mimicking the symptoms of brain chemotherapy seen in humans. Gender factor: Women appear disproportionately affected by brain chemotherapy, and researchers are investigating why.
Source: Virginia Tech
Cancer is quite a challenging diagnosis, but many patients receive a second blow even as they recover: “chemo brain.”
Also called “brain fog,” this combination of cognitive problems (memory problems, difficulty finding words, inability to concentrate) affects up to three out of four cancer patients, according to multiple studies. For many, the effects last years beyond cancer treatment.
A new study offers new models for studying the causes of brain chemotherapy and points to the effects of chemotherapy drugs on the brain’s lymphatic system, which is a network of small vessels in the brain’s protective membranes that help remove waste and transport immune cells.
The study was published October 13 in Communications Biology.
“There is now compounding evidence that these meningeal lymphatics are involved in cognitive problems, including Alzheimer’s disease and also traumatic brain injury,” said co-corresponding author Jennifer Munson, professor and director of the Fralin Biomedical Research Institute at the VTC Cancer Research Center in Roanoke.
“Women are affected by chemotherapy brain fog, or brain fog, much more than men when they are treated with very common chemotherapies, such as those regularly used in breast cancer patients.”
The study highlights considerations for cancer treatment beyond eradicating the cancer itself, said Monet Roberts, assistant professor of biomedical engineering and co-corresponding author of the paper.
“Our study is important because it explores a very real hidden layer of chemotherapy treatment that leaves lasting scars in the daily lives of those living with or who have survived cancer,” said Roberts, a former postdoctoral associate who trained in Munson’s lab at the Fralin Biomedical Research Institute and now continues to study the lymphatic system in her own lab.
Munson and his team developed a three-level modeling system, using a combination of mouse and tissue models, to study changes in the lymphatic system. The in vitro model is the first human tissue engineering system that replicates this unique tissue and has potential for therapeutic testing, patient-specific analysis, and disease-specific incorporation.
The study examined the effects of two of the most common chemotherapy drugs, docetaxel and carboplatin. While both showed impacts on the lymphatic system, they were much more pronounced with docetaxel.
“What we see is a reduction in lymphatic vessels and fewer loops or branches in the vessels,” said Munson, who is also a professor in the Department of Biomedical and Mechanical Engineering at Virginia Tech.
“These are signs of reduced growth that indicate that the lymphatic vessels are changing or not regenerating in a beneficial way. Lymphatic health actually decreased in all three models measured in different ways.”
As anticipated, brain imaging showed reduced lymphatic system drainage in mice. When the research team performed cognitive tests, they discovered that if a mouse had been treated with docetaxel, it had poor memory.
Taken together, Munson said, the results suggest that brain chemotherapy could be the result of poor drainage of the lymphatic system in response to chemotherapy.
“That could explain some of these memory deficits, which is similar to what we’ve seen in Alzheimer’s disease,” Munson said.
“The first step is knowing,” he said. “And now the hope is to figure out how to help. Could giving something pharmaceutical, like a protein, alleviate the problem and not interfere with chemotherapy? We know of other things that also affect flow in the brain, like sleeping better and exercising.”
Munson is also interested in exploring gender differences in the prevalence of brain chemotherapy.
“Lymphatic diseases in general affect women more than men,” he said. “We’re very interested in trying to understand that difference and why it might exist.”
“Ultimately, this work underscores the need to consider not only survival, but also the often overlooked, long-term neurological side effects of cancer treatment on cognitive well-being and quality of life,” Roberts said, “especially in women who are disproportionately affected by these long-lasting side effects.”
Key questions answered:
A: The study suggests that chemotherapy disrupts the brain’s lymphatic drainage system, causing waste buildup and cognitive decline.
A: Both docetaxel and carboplatin affect the lymphatic system, but docetaxel shows more pronounced and long-lasting damage.
A: Researchers are exploring pharmaceutical and lifestyle interventions, such as sleep and exercise, to restore healthy brain flow and reduce cognitive symptoms.
About this chemotherapy and brain chemo news
Author: Juan Pastor
Source: Virginia Tech
Contact: John Pastor – Virginia Tech
Image: Image is credited to Neuroscience News.
Original research: Open access.
“Demonstration of chemotherapy-mediated changes in meningeal lymphatics in vitro, ex vivo, and in vivo” by Jennifer Munson et al. Communications Biology
Abstract
Demonstration of chemotherapy-mediated changes in meningeal lymphatics in vitro, ex vivo and in vivo
Systemic chemotherapy often affects cells beyond the tumor, raising concerns about its impact on peripheral tissues, including the central nervous system (CNS).
Meningeal lymphatic vessels drain cerebrospinal fluid from the CNS to the deep cervical lymph nodes, aiding in immunosurveillance and connecting the CNS to the periphery.
They have been implicated in a number of brain-related disorders whose alterations exacerbate cognitive deficits.
However, in vivo, distinguishing between direct and indirect effects of systemic chemotherapy on meningeal lymphatic vessels remains very challenging, making it difficult to isolate the specific impact on the CNS.
To address this, we present two models we have developed that allow the examination of changes at the cellular and tissue level to study the effects of systemic chemotherapy on meningeal lymphatics.
Our representative in vitro tissue-engineered model of the lumen of a meningeal lymphatic vessel shows cellular alteration, while our ex vivo model culturing mouse meningeal layers investigates structural changes in a controlled environment.
Finally, we correlate functional outcomes with changes observed in vivo and show that systemic taxane chemotherapy leads to morphological changes in meningeal lymphatic vessels, a tendency toward reduced flow through the brain, and impaired cognition, emphasizing the need for further studies on off-target impacts in the CNS and the value of multi-model approaches.
