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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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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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