Caleb Sooknanan ‘20

Aging is often associated with increased neurological problems among humans, and more research is needed to understand how lymphatic vessels connecting the brain and the immune system affect conditions such as Alzheimer’s disease. Doctor Jonathan Kipnis and researchers from the University of Virginia enhanced the lymphatic vessels of aging mice and significantly improved their abilities to learn and retain memory. The researchers treated mice with a specific growth factor that improved the lymphatic drainage of waste molecules from each subject’s cerebrospinal fluid, thereby improving cognitive performance. The researchers also suggested that lymphatic vessel obstruction in mice could augment the effects of Alzheimer’s disease, such as the buildup of plaque within the brain.

To perform the study, the researchers obtained and anesthetized — using a specific solution of ketamine and xylazine — male and female wild-type mice. A pressure sensor catheter was used to measure each subject’s intercranial pressure, while specific injection and photoconversion techniques were used to remove the lymphatic vessels from each brain’s meninges. The researchers then incorporated vascular endothelial growth factor C into the treated mice to proceed with analysis measures. Such measures included photoacoustic imaging for detecting ultrasonic emissions from each subject’s body, neutrophil-to-lymphocyte ratio tests to analyze each subject’s immune system, and cerebrospinal fluid tests for understanding the changes in macromolecule amounts within lymphatic vessel environments.

The researchers found that when mice were exposed to vascular endothelial growth factor C, more macromolecules were removed from the cerebrospinal fluid through each subject’s lymphatic vessels. From the study’s results, the researchers reasoned that the obstruction of meningeal lymphatic vessels for Alzheimer’s disease models among mouse subjects could cause the release of amyloid-β — a series of peptides known as the main components of the plaques associated with Alzheimer’s disease — into the meninges. These observations related to those of human meningeal diseases, but more research is needed to understand lymphatic vessel behavior among humans and create an appropriate drug for lymphatic drainage. Additionally, more research is needed to determine whether age-related lymphatic vessel changes could abrupt current treatments for Alheimer’s disease. These findings, the researchers suggest, may allow scientists to delay the progression of age-based diseases among patients.

References

1. J. Kipnis, et. al., Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature (2018). doi: https://doi.org/10.1038/s41586-018-0368-8.  
2. Image retrieved from: https://upload.wikimedia.org/wikipedia/commons/7/7e/Human_brain_lateral_view.JPG