Chemotherapy Drug Linked to Lymphatic Changes in the Brain’s Protective Layers and “Chemo Brain” Symptoms

A new study from Virginia Tech and the University of Virginia is shedding light on why some cancer patients experience cognitive problems long after chemotherapy. Published in Communications Biology, the research reveals that the widely used chemotherapeutic drug docetaxel can alter the structure and function of the meningeal lymphatic vessels—a drainage network that helps clear waste from the brain and supports immune surveillance.

Using a three-tiered approach combining in vitro, ex vivo, and in vivo models, investigators demonstrated that docetaxel—but not carboplatin—causes significant disruption to these delicate vessels. The findings suggest that the brain’s own waste-clearing system may be a previously overlooked target of chemotherapy, potentially contributing to the constellation of symptoms known as chemotherapy-related cognitive impairment, or “chemo brain.”

To isolate chemotherapy’s impact on the meningeal lymphatics, the research team first created an engineered human cell model that mimicked a lymphatic vessel’s lining. When exposed to docetaxel, these cells showed marked structural disorganization, with impaired ability to maintain barrier integrity and reduced proliferation, whereas carboplatin had minimal effect. This pointed to a drug-specific vulnerability of lymphatic endothelial cells.

Next, in mouse tissue cultures, the same docetaxel exposure caused regression of lymphatic vessel features, including a decrease in branching and “intussusceptions,” small looping structures associated with vessel remodeling. These morphological changes were confirmed in living mice, where systemic docetaxel treatment led to narrower meningeal vessels and fewer branching points, findings absent in carboplatin-treated animals.

To explore the functional implications, tumor-free mice received systemic docetaxel and underwent behavioral testing. Compared with control animals, treated mice displayed deficits in learning and memory, performing poorly on both passive avoidance and novel object recognition tasks. Magnetic resonance imaging revealed a trend toward reduced cerebrospinal fluid flow in key cognitive regions, including the hippocampus and prefrontal cortex—changes that correlated with the degree of lymphatic vessel disruption.

While the phenomenon of “chemo brain” has long been recognized, its biological basis remains elusive. This study provides some of the clearest evidence to date that chemotherapy can harm non-tumor tissues linked to brain health. The findings also align with prior work showing that meningeal lymphatic dysfunction exacerbates conditions like Alzheimer’s disease and traumatic brain injury.