Inhibiting Cyclin B1-treated Pontine Infarction by Suppressing Proliferation of SPP1+ Microglia.

Ming Luo, Zhihua Qiu, Xiangyue Tang, Li Wu, Shaojun Li, Juehua Zhu, Yongjun Jiang

Molecular neurobiology 2023 Apr

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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. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Ming Luo, Zhihua Qiu, Xiangyue Tang, Li Wu, Shaojun Li, Juehua Zhu, Yongjun Jiang. Inhibiting Cyclin B1-treated Pontine Infarction by Suppressing Proliferation of SPP1+ Microglia. Molecular neurobiology. 2023 Apr;60(4):1782-1796