A naturally occurring molecule that helps the brain clear away damaged blood cells could open the door to new treatments for one of the deadliest forms of stroke, research led by University of Manchester scientists suggests.
A naturally occurring molecule that helps the brain clear away damaged blood cells could open the door to new treatments for one of the deadliest forms of stroke, research led by University of Manchester scientists suggests.
Intracerebral haemorrhage (ICH) occurs when a blood vessel bursts and bleeds directly into the brain, leaking substances such as iron that cause serious damage for which effective treatments remain limited.
Publishing in the Journal of Neuroinflammation, the researchers have now identified a biological process in humans and mice that appears to help the brain deal with the aftermath of the bleeding and improve recovery.
The Medical Research Council funded study focused on an enzyme called cholesterol 25-hydroxylase (CH25H) which converts cholesterol into a molecule called 25-hydroxycholesterol (25HC).
They found increased levels of CH25H in brain tissue from people who had suffered ICH, particularly in immune cells surrounding the site of the bleed.
CH25H also appeared to help the brain's resident immune cells called microglia to engulf and remove red blood cells released into brain tissue following a haemorrhage.
And it influenced genes involved in clearing cellular debris and processing fats and cholesterol within the microglia.
The clean-up process can be critical because when red blood cells break down they can contribute to further brain damage after the initial stroke.
Mice genetically lacking Ch25h experienced greater iron accumulation and tissue damage, alongside worse neurological symptoms following an experimentally induced brain haemorrhage.
By contrast, treating mice with 25HC improved their functional recovery and reduced signs of damage in the brain.
When Ch25h was absent, immune cells were less effective at engulfing red blood cells and accumulated more fatty droplets inside them.
Treatment with 25HC increased the mice cells' ability to engulf red blood cells while reducing the build-up of fatty droplets, providing further evidence for the effect.
Co-lead author Professor Catherine Lawrence from The University of Manchester, said: "Our research suggests that the enzyme CH25H and the molecule it produces, 25HC, help the brain's immune cells clear away damaged red blood cells after a haemorrhagic stroke, limiting the harmful effects of bleeding and highlighting a promising natural process that could potentially be harnessed to improve recovery for patients."
Co-lead author Dr Paul Kasher said: "These findings reveal an important part of the brain's natural clean-up response after haemorrhagic stroke, showing how 25HC can help immune cells remove damaging material more effectively, and while further research is needed, targeting this pathway could ultimately offer a new approach to treating this devastating and often deadly condition.
"Further research will be needed to establish whether targeting this pathway could eventually be developed into a safe and effective treatment for patients."
- The paper: Ch25h/25HC axis orchestrates phagocytosis and lipid metabolism after intracerebral haemorrhage is published in the Journal of Neuroinflammation and available here DOI 10.1186/s12974-026-04106-5
