Spi1 Regulates the Microglial/macrophage Inflammatory Response Via the PI3K/AKT/mTOR Signaling Pathway After Intracerebral Hemorrhage

Overview

Journal Neural Regen Res

Date 2023 Jul 25

PMID 37488863

Authors

Guoqiang Zhang

Jianan Lu

Jingwei Zheng

Shuhao Mei

Huaming Li

Xiaotao Zhang

An Ping

Shiqi Gao

Yuanjian Fang

Jun Yu

Affiliations

Soon will be listed here.

Abstract

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage. The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation. However, the effect of Spi1 on intracerebral hemorrhage remains unclear. In this study, we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome. We showed that high Spi1 expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis, glycolysis, and autophagy, as well as debris clearance and sustained remyelination. Notably, microglia with higher levels of Spi1 expression were characterized by activation of pathways associated with a variety of hemorrhage-related cellular processes, such as complement activation, angiogenesis, and coagulation. In conclusion, our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage. This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

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