In short:
- Monash scientists are helping to pioneer a new, non-invasive approach to treating stroke by boosting the brain's natural waste-clearing system – its lymphatic network
- The treatment helps neck lymphatic vessels pump more effectively, improving the clearance of waste products from the brain after a stroke
- Early imaging studies have revealed differences between male and female brain-draining lymphatics, paving the way for more tailored treatments for conditions like stroke and Alzheimer's that disproportionately affect women
Scientists from Monash University are partnering with colleagues at the Yale School of Medicine in New Haven, Conn., to develop a new, high-tech approach for treating ischemic stroke by enhancing removal of toxic waste products from the brain.
The "brain-draining lymphatics" are a set of drainage pathways that clear waste from the brain, with dysfunction of this "clean-up and drainage network" linked to Alzheimer's disease and other neurological and neurodegenerative diseases (NNDs).
The work is being done in collaboration with faculty at Yale School of Medicine, including Anne Eichmann, PhD, Lindsay McAlpine, MD, and Jean-Leon Thomas, PhD.
It was the Yale team who originally found that improving brain-draining lymphatic function can boost recovery following ischemic stroke. Together, Yale and the Monash Institute of Pharmaceutical Sciences (MIPS) are now developing non-invasive devices that help the neck's lymphatic vessels pump more effectively, improving the clearance of excess fluid and harmful waste from the brain right after stroke has occurred – at a time when every second counts.
The researchers are also using advanced imaging techniques to study the brains of 140 participants. Initial studies have found that women have less lymphatic vessel coverage in the brain's outer layer compared to men, potentially leading to less efficient waste drainage and explaining why women are at higher risk or have worse outcomes for many NNDs, including stroke and Alzheimer's disease.
This information will be used to explore sex-specific treatments for NNDs which disproportionately affect women, including stroke and Alzheimer's.
The Monash lead of the Advanced Research Projects Agency for Health (ARPA-H)-funded project, Professor Natalie Trevaskis from MIPS, said that since the project inception a year ago the team has made significant strides in building on current evidence in this relatively new area of research. "For decades, the brain was considered to be devoid of a lymphatic system. It wasn't until 2015 that two separate teams discovered lymphatics in the brain's outer layer transport fluid and waste products from the brain to lymphatic vessels in the neck," Professor Trevaskis said.
"We now know that this system plays a crucial role in keeping the brain healthy. By boosting this natural clean-up system, we hope to change how ischemic stroke and other NNDs are treated."
Professor Trevaskis added that the Yale team's findings, which help explain why women might be more affected by diseases like stroke and Alzheimer's, opens up a new roadmap to develop treatments that take biological sex into account.
Yale's Professor Anne Eichmann, Co-Director of the Yale Cardiovascular Research Centre and project co-lead said "We are excited to investigate brain fluid clearance in healthy volunteers across sex and age and develop therapeutics that can enhance brain waste clearance and promote recovery from stroke.
"By understanding the subtle differences in how men's and women's brains clear waste, we can design therapies that are more precise, effective and equitable."
The ARPA-H project has a particularly strong focus on ischemic stroke due to its prevalence - it impacts around a quarter of women at some stage in their life and is the second leading cause of death globally.
Current treatments involve intravenously administering "clot-busting" drugs or removing clots using specialised equipment. These approaches have limitations and need to be administered within a few hours following the stroke in order to be effective.
"While current treatments can be very effective, they are associated with significant risk of bleeding and there can be several barriers limiting people's access to them in a timely manner - particularly the requirement for a well-equipped medical facility and team - our goal is to overcome these barriers to access," Professor Trevaskis said.
"The ultimate goal is to develop new therapeutic technologies that enhance lymphatic removal of toxic waste products from the brain following stroke, which can aid more effective recovery and reduce ongoing disability such as difficulty speaking, walking and completing everyday activities."
