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Latest publication 02/20/2026

Ch25h and 25HC axis orchestrates phagocytosis and lipid metabolism after intrace

Intracerebral haemorrhage (ICH) is a devastating form of stroke for which therapies are lacking. Secondary brain injury driven by erythrocyte lysis...

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    [title] => Ch25h and 25HC axis orchestrates phagocytosis and lipid metabolism after intrace
    [paragraph] => Ch25h and 25HC axis orchestrates phagocytosis and lipid metabolism after intracerebral haemorrhage
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Authors
Catherine B. Lawrence, Ran Zhou, Victor Tapia, Abigail Bennington, Ruyue Gao, Milo Elmes, I-Hsuan Lin, Ziyu Dai, Siohban Crilly, Caroline Pot, Stuart Allan, Paul Kasher


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Abstract
Intracerebral haemorrhage (ICH) is a devastating form of stroke for which therapies are lacking. Secondary brain injury driven by erythrocyte lysis contributes to poor outcomes, highlighting the need to enhance endogenous haematoma clearance. Here, we identify cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25HC) as key regulators of phagocytic and lipid-handling responses after ICH. CH25H expression was increased in postmortem human ICH tissue and a mouse ICH model, localising predominantly in perihaematomal phagocytes. Ch25h deficiency in mice exacerbated blood-brain barrier disruption, iron deposition, and neurological deficits after ICH. Conversely, 25HC treatment improved functional recovery and reduced tissue pathology. Single-cell RNA sequencing revealed selective upregulation of Ch25h in activated microglia after ICH, which modulated phago-lysosomal and lipid metabolic gene expression. Consistently, 25HC enhanced erythrocyte phagocytosis and limited lipid droplet accumulation in vitro. Together, these findings identify CH25H/25HC-dependent lipid reprogramming as a critical determinant of phagocyte function and neurological recovery after ICH.

Keywords/Topics
mice; grip strength; ch25h 25hc axis; phagocytosis; lipid metabolism; intracerebral haemorrhage intracerebral haemorrhage; stroke; which; therapies; secondary brain injury

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.

New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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