Inhibiting Cyclin B1-treated Pontine Infarction by Suppressing Proliferation of SPP1+ Microglia.
Mol Neurobiol
; 60(4): 1782-1796, 2023 Apr.
Article
en En
| MEDLINE
| ID: mdl-36572839
ABSTRACT
Pontine infarction is the major subtype of brainstem stroke causing severe neurological deficits. The pathophysiology and treatment of pontine infarction was rarely studied. A rat model of acute pontine infarction was established via injection of endothelin-1 in the pons. Single-cell RNA sequencing was applied to detect the cellular response in pontine infarction. Based on this finding, a potential treatment for pontine infarction targeting microglia was verified. Occlusion of penetrating artery caused by endothelin-1 led to pontine infarction. Single-cell RNA sequencing revealed a subtype of activated microglia, SPP1+ microglia, which were different from M1-like or M2-like depolarization. SPP1+ microglia interacted with oligodendrocytes and contributed to the demyelination of nerve tracts. Cyclin B1 regulated the proliferation of SPP1+ microglia. Cucurbitacin E, a cyclin B1 inhibitor, reduced the proliferation of SPP1+ microglia around the injured myelin sheath and alleviated the demyelination. Moreover, cucurbitacin E treatment decreased the ischemic infarction volume and neurological deficits after pontine infarction. SPP1+ microglia contributed to axonal demyelination in the pontine infarction, and inhibition of SPP1+ microglia provided neuroprotection for pontine infarction.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Desmielinizantes
/
Infartos del Tronco Encefálico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China