The latest treatment method prevents brain diseases due to weakness of the lymphatic system

 

Like the human body's lymphatic system, the human brain's glymphatic system removes accumulated metabolic wastes and distributes nutrients and other compounds within the brain. The glymphatic system filters the accumulated toxins in the brain and removes them from the brain, and this system, which is active during sleep, remains inactive during the waking period.

Disorders in the functioning of the glymphatic system are the primary causes of neurological diseases and stroke. In the United States of America, belonging to the state of Missouri, St. A group of researchers from the Washington University McKelvey School of Engineering located in St. Louis recently managed to find a non-pharmacological and non-invasive treatment that uses a method called focused ultrasound that can increase the function and circulation of the glymphatic system. The Proceedings of the National Academy of Sciences (PNAS), published on May 15, posted the information about this treatment method discovered by this research group for the first time. Using this method to study brain-related diseases and brain function further has become one of the main objectives of these researchers.

Hong Chen, associate professor of biomedical engineering in McKelvey Engineering and of neurological surgery in the School of Medicine, and Dezhuang (Summer) Ye, a postdoctoral research associate, and Si (Stacie) Chen, a former postdoctoral research associate, developed the Focused ultrasound method and The research has been done using the technique called FUSMB, which uses circulating microbubbles. In this research, it had discovered that the transport process of the glymphatic system could be improved mechanically. Here the brains of mice have been used to carry out these experiments.

This focused ultrasound method can penetrate the skull, reach the brain, and target a specific region in the brain. In previous studies, Professor Chen's team found that microbubbles injected into the blood vessels amplify the effect of ultrasound waves, thereby affecting the blood vessels' blood-pumping process. It helps agents delivered intravenously through the blood vessels, such as drugs or gene therapy, accumulate in the brain.

"Through intranasal delivery, it provides a new and non-invasive way to investigate the glymphatic pathway in the brain," added Professor Chen. But the ability to do so is currently limited by the fact that non-invasive approaches to the glymphatic system have yet to discover. In this research, they administered a fluorescent tracer intravascularly to three groups of experimental mice. Then, after injecting microbubbles, they aimed focused ultrasound waves deep into the thalamus, the administrative part of the brain. So when they used a technique called FUSMB to 3D image the brain tissue on the treated side, they found that it increased the transport of the tracer in the perivascular space.

They compared the efficacy of combinations of three control methods: focused ultrasound, microbubbles and tracer in relation to these three groups. All mice in the three control groups showed low tracer accumulation, and the research team confirmed that treatment with microbubble and focused ultrasound increased tracer transport. To further ensure these results, this FUSMB treatment method has also been used after injecting tracers directly into the cerebrospinal fluid, an invasive treatment method commonly used today.

They found that FUSMB therapy, which uses focused ultrasound, doubled or tripled the transport of tracers through the targeted part of the brain compared to the non-targeted part. It confirms to the research team that no matter which method of tracer administration uses, the intranasal method or injection, the glymphatic transport improves in every case in the FUSMB treatment method. Also, examining the microscopic photographs taken in the brain of mice used in this research using confocal microscopy and the data obtained related to brain tissue clearance proves that this FUSMB method improved the glymphatic transport through selected protein agents.

Here, the research team studied the delivery of the tracer using both intranasal and injection routes. In doing so, an increase in glymphatic transport of tracers observe along all blood vessels: arteries, capillaries and veins. Meanwhile, they found that the fluorescence intensity along arteries was higher than in capillaries and veins.

"This study demonstrates the feasibility of using ultrasound combined with microbubbles as a non-invasive and non-pharmacological approach to manipulate glymphatic transport," said research assistant Dezhuang Ye, who contributed to the study. Through this treatment method using microbubbles, it will be possible to improve the ability to remove accumulated waste in the brain and to reduce the various disease conditions that occur in the brain due to the weakness of the glymphatic system.

Meanwhile, Professor Hong Chen and the research team are currently studying how this non-invasive and non-pharmacological method can use to fight neurological diseases such as Alzheimer's and Parkinson's—also said.