ATP11C as a key regulator of neuronal loss following intracerebral hemorrhage in mice.

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Tác giả: Jiyuan Bu, Chang Cao, Gang Chen, Haiying Li, Lianxin Li, Lu Peng, Qing Sun, Zhong Wang, Zilan Wang, Feiyang Zhang

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Biochemical and biophysical research communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 708123

Intracerebral hemorrhage (ICH) is a severe form of stroke with high rates of mortality and morbidity. Neuronal loss following ICH is a critical factor influencing patient outcomes. Emerging evidence suggests that microglial phagocytic activity is enhanced after ICH, yet its role in neuronal loss remains unclear. In this study, we observed microglia engulfing viable neurons, characterized by high NeuN signals or intact nuclear morphology, in the perihematomal region of a murine autologous blood injection ICH model. This phenomenon was also observed in an in vitro ICH model, where microglia engulfed neurons in a neuron-microglia co-culture system treated with oxyhemoglobin. Furthermore, we found that oxyhemoglobin exposure induced phosphatidylserine (PS) externalization in non-apoptotic (PI-) neurons and led to a downregulation of the PS flippase ATP11C. Notably, lentivirus-mediated overexpression of ATP11C in neurons specifically prevented the ICH-induced decline in ATP11C levels and inhibited microglial engulfment of neurons. Furthermore, ATP11C overexpression significantly improved neurological outcomes in the mouse ICH model. These findings offer new insights into the mechanisms of neuronal loss after ICH, positioning ATP11C as a promising therapeutic target for attenuating brain injury by regulating PS externalization in neurons.
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