Chemotherapy, anti-cancer drugs that stop the growth of tumor cells, encompasses a wide variety of different agents. Some chemotherapeutic agents work by directly killing cancer cells, while others prevent malignant cells from further dividing. Most chemotherapies target rapidly dividing cells, including cancer cells, but this can result in the death of healthy cells as well, underscoring a significant adverse effect of these life-saving drugs.
Recently, oncologists have recognized a side effect of chemotherapy treatment directed at the central nervous system (CNS), particularly at cells in the brain. The impact of chemotherapy on the brain results in notable cognitive issues, including loss of memory, having a hard time articulating thoughts into words, and impaired concentration. These clinical manifestations, commonly referred to as “chemo brain,” may begin during treatment, but can linger long after a patient ends chemotherapy, thus potentially negatively affecting the quality of life of cancer survivors. Literature suggests more than 70% of cancer patients experience chemo brain at some point during or after cancer treatment.
While clinicians have recognized chemo brain and the associated symptoms, the mechanisms by which chemotherapy and its effects transfer between the CNS and the periphery remain unclear. Lymphatics located in the meninges, the protective tissues lining the brain and spinal cord, drain fluid from the CNS, where it can circulate through lymph nodes elsewhere in the body. To address the role of systemic chemotherapy on the meningeal lymphatics, a team of researchers conducted a comprehensive pre-clinical study. The results of the study, recently published in Communications Biology, demonstrate a role of the meningeal lymphatic system in the onset of chemo brain.
The researchers developed a novel modeling system, using pre-clinical tissue-engineered and mouse models, to study the meningeal lymphatics and their role in the onset of chemo brain. First, the researchers developed an in vitro tissue-engineered system that closely mimics the unique tissue of the meningeal lymphatic system. Next, an ex vivo model involving the culture of mouse meningeal layers allows researchers to observe structural changes. Finally, in vivo studies using mouse models demonstrate a link between systemic chemotherapy and morphological changes in the meningeal lymphatics.
The study reveals that chemotherapy induces alterations in the meningeal lymphatics, resulting in cognitive dysfunction. The pre-clinical research presented in this study lays the groundwork for further investigation into the unintended effects of chemotherapy on the CNS. Furthermore, this research underscores the urgent need to incorporate plans for long-term cognitive support and treatment into cancer care regimens.
Sources: Adv Cancer Res, Commun Biol