Han Hongbin's team proposed a new theory of extracellular space neural regulation, developed a new technology for extracellular space molecu

Release date: August 21, 2024 Views:

Recently, the journal Science China: Life Sciences published online the research results of Professor Han Hongbin's research team from Peking University.

Stroke is the second leading cause of death in the world and the leading killer of Chinese people. In the past two decades, Han Hongbin's team has been committed to the diagnosis and treatment of major brain diseases through the extracellular space (ECS) of the brain. The brain ECS occupies 15% to 20% of the volume of the living brain, far exceeding the 3% to 5% occupied by cerebral blood vessels that have been highly valued in the past; the transport of molecules in the ECS is closely related to brain functional activities such as sleep, memory and sensory formation. The brain ECS not only plays an important role in the occurrence and development of encephalopathy, but is also the only way for drugs to reach the target of nerve cells and exert their effects after entering the brain parenchyma. The blood-brain barrier has greatly hindered the development of new stroke drugs via the vascular route. Drug administration via the brain ECS route can effectively bypass the blood-brain barrier and exert its effects directly in the brain, providing a new direction for the treatment of brain diseases.

Schematic diagram of the mechanism of m-EAI in treating ischemic stroke

A. After a stroke occurs, various types of cells in the central nervous system will undergo different morphological changes. Neurons in the infarct core area are most affected, their cell bodies and axons disappear, and glial cells usually show cell swelling. Neurons in the ischemic penumbra area are called "ischemic neurons" and are relatively viable. Microglia and astrocytes can be transformed into an "activated state" and produce proinflammatory cytokines. B. m-EAI can accelerate the drainage of ISF in the ischemic penumbra area, promote the clearance of proinflammatory cytokines, and further reduce the activation of glial cells, thereby saving neurons in the ischemic penumbra area. Credit: ©Science China

Ten years ago, the team published a research paper in SCIENCE CHINA Life Sciences magazine, proposing a new drug delivery technology through the brain ECS route - simple diffusion delivery (SDD). This technology overcomes the two major technical bottlenecks of drug backflow and difficulty in accurate quantitative analysis in convection enhanced delivery (CED). The study found that by using the SDD method, only 1/800 of the dosage of the neurological drug citicoline in the traditional drug delivery method was used to achieve more than 6 times the neuroprotection range in the ischemic area. This is also the first time that the possibility and effectiveness of minimally invasive drug delivery through the ECS route have been confirmed for the treatment of ischemic stroke. Since both SDD and CED are invasive drug delivery, solving the invasiveness of this method is the key to achieving practical application in clinical transformation.

After 13 years of scientific and technological research, the team finally solved this technical problem and proposed and established a minimally invasive and safe modified epidural artery implantation (m-EAI). In previous studies, the team has confirmed the accelerating effect of EAI on the drainage of interstitial fluid (ISF) in the brain ECS. In this study, the accelerated effect of the modified EAI (m-EAI) on brain tissue fluid drainage was confirmed again, and the modified method enabled EAI at different time points after ischemia to achieve dynamic control of the accelerated effect of ISF drainage. The new method not only does not require puncture to destroy the dura mater, but also provides the same neuroprotective effect as SDD. Studies have confirmed that this neuroprotective effect is achieved by reducing the accumulation of proinflammatory cytokines such as IL-6, IL-1β and TNF-α in the brain ECS. The acceleration of ISF drainage not only reduces the local inflammatory response in the ischemic area, but also slows down the excessive activation of microglia and astrocytes.

In summary, this study proposed a new method for treating ischemic stroke by regulating ECS molecular transport. It is particularly noteworthy that this minimally invasive method achieves neuroprotection in the ischemic area without using any neuroprotective drugs. Therefore, the study on the neuroprotective effect of combined use of m-EAI and neuroprotective drugs on ischemic stroke is particularly worth looking forward to. At the same time, this study also verified the theoretical hypothesis that inflammatory response is the cause of aggravated neural damage in the ischemic area of stroke.

For details of the study, please see the original article:

A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid（ http://engine.scichina.com/doi/10.1007/s11427-024-2592-4 ）

This article is reproduced from https://www.eurekalert.org/news-releases/1055093