Early research suggests that “chemobrain” – difficulties with concentration, thinking and memory caused by chemotherapy – may be caused by the destruction of the brain’s lymphatic system caused by cancer treatment.
This study focused on the meningeal lymphatic vessels, a drainage network found in the protective tissue layers surrounding the brain. Dysfunction of this network is associated with Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury.
you may like
Using human and mouse cells, as well as live laboratory mice, researchers found evidence that taxanes, a common type of chemotherapy drug that inhibits cancer cell division, damage lymphatic vessels in the brain and limit lymphatic drainage. Normally, blood vessels work with the brain’s glymphatic system to flush out metabolic wastes.
“Lymph health actually decreased in all three models when measured using different methods,” study co-author Jennifer Munson, director of the Virginia Tech Cancer Research Center in Roanoke, Virginia, said in a statement. The blood vessels shrank and the number of branches decreased, she said, “a sign of reduced growth that indicates the lymph vessels are changing or not regenerating in a beneficial way.”
“Chemobrain” is a broad category of cognitive changes that occur after chemotherapy and can last for years after treatment. “There’s so much we don’t know,” Manson told Live Science, but these cognitive impairments have previously been linked to oxidative stress, inflammation, and impaired myelination. (Myelin is the fatty insulation that covers nerve fibers.)
“We wanted to focus on the meningeal side because other researchers were looking at the neural side,” Munson said.
To do this, Manson and her team used three models: human cells, mouse tissue, and live mice to assess whether chemotherapy drugs cause changes in meningeal lymphatic vessels at different scales.
First, we used cell lines to construct a human cell model of healthy meningeal lymphatic vessels. This model combined cells from the lining of lymphatic vessels with meningeal cells. This allowed the research team to elucidate the individual effects of chemotherapy on each cell’s function. They also cultured healthy mouse meningeal tissue in laboratory dishes to assess structural changes caused by drug exposure.
They found that the drug docetaxel destroyed cells by reducing their range and length in a human meningeal lymph model. The treatment also shrunk blood vessels in the mouse tissues and reduced the number of loops within the network structure.
you may like
The researchers then conducted experiments on live mice, comparing mice treated with docetaxel to mice that were not exposed to the drug. Mice with cancerous tumors that received the drug tended to have narrower meningeal lymph vessels and fewer loops than untreated mice.
The researchers wanted to see if these structural changes caused by docetaxel led to memory impairment or behavioral changes. They found that healthy mice given docetaxel forgot things they had previously seen, while mice that were not given showed clear signs of remembering them. MRI scans of treated mice showed that these cognitive problems were correlated with decreased fluid flow through lymph vessels, the authors wrote in the study.
Professor Munson cautioned that this was early stage research and many gaps remained in our understanding of the link between ‘chemobrain’ and meningeal lymphatic vessels. He explained that one of the study’s limitations is that chemotherapeutic drugs are given over a relatively short period of time, whereas chemotherapy courses for human cancer patients often span several months.
Similarly, the memory deficits experienced by the mice were tested over several days, whereas humans can experience chemical brains for years after treatment. “So these lasting effects that we’re seeing are [human] “Patients may have different mechanisms and we may not fully understand them here,” Manson said.
Manson said it will be important to replicate this study using samples taken from a large number of individuals at different ages and compare the results in mice with tumors and those without tumors to see if there is a difference in how chemotherapy affects the mice. Ultimately, she hopes this research will provide new targets to treat this side effect of chemotherapy.
“Ultimately, this study highlights the need to consider not only survival but also the long-term, often overlooked neurological side effects of cancer treatment on cognitive health and quality of life,” study co-author Monet Roberts, assistant professor of biomedical engineering and mechanics at Virginia Tech, said in a statement.
This article is for informational purposes only and does not provide medical advice.
Source link
