Stroke can strike without warning, threaten life, and, even after recovery, leave aftereffects such as paralysis or speech disorders. In particular, ischemic stroke, or cerebral infarction, which occurs when a cerebral blood vessel is blocked, has a better prognosis the faster it is treated, but in reality, the golden hour is often missed.
Lee Chang-jun and researchers with the Institute for Basic Science (IBS) Center for Cognition and Sociality said on the 28th that, together with Eulji University researchers, they uncovered a new mechanism for how brain damage progresses after a stroke and, through animal experiments, identified a potential new drug candidate that can stop it. The findings were published the same day in the international journal Cell Metabolism.
Astrocytes are a type of glial cell that make up a large proportion of the brain. As their name suggests, they are star-shaped and, under normal conditions, support neurons and keep the brain environment stable. It has been known that when a stroke occurs, they form a "glial scar" around the damaged area to prevent the lesion from spreading further.
However, this study found that this barrier does not always act protectively. When hydrogen peroxide surges after a stroke, astrocytes are stimulated to produce type I collagen. Although collagen is well known as a protein that makes up skin, bone, and connective tissue, in the context of stroke it can accumulate around astrocytes, encase neurons, and act as a factor that worsens damage.
Based on this mechanism, the team tested an in-house developed drug candidate, "KDS12025." The compound is designed to reduce hydrogen peroxide and suppress collagen production.
In a mouse model of stroke, administration of KDS12025 markedly reduced glial scar formation and neuronal cell death. Motor function, which had declined due to stroke, recovered to near normal within a week. Notably, recovery of neurological function was observed even when it was administered two days after the stroke.
The researchers also confirmed the effect of KDS12025 in a primate model. Three days after administration, the lesion size decreased, and after one week, the previously paralyzed hand function recovered. In a fruit-grabbing test, the treated monkey succeeded in all 10 attempts.
Eulji University Professor Yoo Seung-jun said, "It is meaningful in that we proposed hydrogen peroxide and collagen as new targets for stroke treatment," and added, "Given that we confirmed therapeutic effects in a primate model, we expect the work could lead to follow-up clinical research."
IBS Director General Lee Chang-jun said, "Through research that linked basic research to new drug development and preclinical validation, we presented both the cause of stroke injury and the possibility of treatment."