Stroke is a disease that occurs when blood vessels in the brain become blocked or burst, causing damage to brain cells, and it can leave severe sequelae even if one survives. Prompt intervention, as well as treatment and rehabilitation, is important. Recently, domestic researchers have developed a treatment targeting astrocytes in the brain, successfully inducing the recovery of motor functions.
The research team led by Director General Lee Chang-jun from the Institute for Basic Science (IBS) collaborated with Professor Kim Hyung-il from the Gwangju Institute of Science and Technology (GIST) and Professor Heo Won-do from the Korea Advanced Institute of Science and Technology (KAIST) to demonstrate that they could enhance the recovery of motor functions after chronic stroke by regulating the calcium signals of astrocytes using optogenetic technology. The research results were published in the international journal Science Advances on the 31st of last month.
Stroke occurs due to various factors such as hypertension, diabetes, and hyperlipidemia, with ischemic stroke, which is caused by blockage or reduction of blood flow to the brain, accounting for the majority. In particular, subcortical strokes, which occur in deep structures below the cortex, represent about 30% of all ischemic strokes and have a poor prognosis.
Currently, neurorehabilitation therapy for stroke primarily uses methods that directly stimulate neurons. These include using strong magnetic fields or attaching electrodes to deliver electric currents. However, these methods have a non-selective effect on all cells in the stimulated area, and their mechanisms of action are unclear, making it difficult to predict treatment outcomes, with significant variability in treatment effects.
The research team attempted a new approach by regulating the calcium signals of astrocytes instead of directly stimulating neurons. Astrocytes are star-shaped non-neuronal cells that make up the majority of the cells in the brain. Researcher Lee Sang-kyu from IBS noted, "Astrocytes play a crucial role not only in supporting neurons but also in significantly affecting neuronal activation and synaptic plasticity," and he explained, "We aimed to reconstruct neural circuits and induce recovery of brain functions by regulating calcium signals in astrocytes."
When calcium signals in astrocytes increase, neurochemical regulators such as ATP and D-serine are secreted, which play important roles in regulating neuronal activation. ATP enhances neuronal excitability, while D-serine enhances synaptic plasticity. Synaptic plasticity is crucial for the recovery of damaged neural circuits after stroke, as it refers to the ability of neural connections to be strengthened and restructured. Additionally, astrocytes regulate glutamate, which is essential for maintaining the balance of neural circuits, preventing excessive neuronal excitation and promoting stable neural activity.
The research team used the optogenetic tool OptoSTIM1, jointly developed by IBS and KAIST in 2015, to regulate calcium signals in mouse brain astrocytes with light. As a result of activating the calcium signals in the astrocytes of the sensorimotor cortex region, which is closely related to motor function recovery, not only were fine motor skills using the forelimbs improved, but overall motor abilities were enhanced. Even low-intensity light stimulation for one hour a day over the course of two weeks led to recovery of motor abilities.
Director General Lee Chang-jun said, "We presented a precise and safe stroke treatment strategy targeting astrocytes," and noted, "This could lead to the development of drugs that regulate calcium signals in astrocytes, which may be applied not only to stroke but also to the treatment of various neurological diseases, including Alzheimer's disease."
References
Science Advances (2025), DOI: https://doi.org/10.1126/sciadv.adn7577