Rapamycin promotes hematoma resorption and enhances endothelial cell function by suppressing the mTOR/STAT3 signaling in chronic subdural hematoma.
Exp Cell Res
; 433(2): 113829, 2023 12 15.
Article
en En
| MEDLINE
| ID: mdl-37879548
Chronic subdural hematoma (CSDH) remains a neurosurgical condition and a healthy burden especially in elderly patients. This study focuses on the functions of rapamycin and its related molecular mechanisms in CSDH management. A rat model of CSDH was induced, which developed significant hematoma on day 5 after operation. The rats were treated with rapamycin or atorvastatin, a drug with known effect on hematoma alleviation, or treated with rapamycin and atorvastatin in combination. The atorvastatin or rapamycin treatment reduced the hematoma development, blood-brain barrier permeability, neurological dysfunction in CSDH rats, and the combination treatment showed more pronounced effects. Human brain microvascular endothelial cells hCMEC/D3 were stimulated by hematoma samples to mimic a CSDH condition in vitro. The drug treatments elevated the cell junction-related factors and reduced the pro-inflammatory cytokines both in rat hematoma tissues and in hCMEC/D3 cells. Rapamycin suppressed the mTOR and STAT3 signaling pathways. Overexpression of mTOR or the STAT3 agonist suppressed the alleviating effects of rapamycin on CSDH. In summary, this study demonstrates that rapamycin promotes hematoma resorption and enhances endothelial cell function by suppressing the mTOR/STAT3 signaling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sirolimus
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Hematoma Subdural Crónico
Límite:
Aged
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Animals
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Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2023
Tipo del documento:
Article