Stromal cell‐derived factor‐1 downregulation contributes to neuroprotection mediated by Yu Wu, Zhuwei Zhang, Xiaoou Sun, Jing Wang, Haitao Shen, Xue Sun, Zhong Wang
CXC chemokine receptor 4 interactions after intracerebral hemorrhage in rats
- Pharmacology (medical)
- Physiology (medical)
- Psychiatry and Mental health
Stromal cell‐derived factor‐1 (SDF‐1) and CXC chemokine receptor 4 (CXCR4) have a substantial role in neuronal formation, differentiation, remodeling, and maturation and participate in multiple physiological and pathological events. In this study, we investigated the role of SDF‐1/CXCR4 in neural functional injury and neuroprotection after intracerebral hemorrhage (ICH).
Western blot, immunofluorescence and immunoprecipitation were used to detect SDF‐1/CXCR4 expression and combination respectively after ICH. TUNEL staining, Lactate dehydrogenase assay, Reactive oxygen species assay, and Enzyme‐linked immunosorbent assay to study neuronal damage; Brain water content to assay brain edema, Neurological scores to assess short‐term neurological deficits. Pharmacological inhibition and genetic intervention of SDF‐1/CXCR4 signaling were also used in this study.
ICH induced upregulation of SDF‐1/CXCR4 and increased their complex formation, whereas AMD3100 significantly reduced it. The levels of TNF‐α and IL‐1β were significantly reduced after AMD3100 treatment. Additionally, AMD3100 treatment can alleviate neurobehavioral dysfunction of ICH rats. Conversely, simultaneous SDF‐1/CXCR4 overexpression induced the opposite effect. Moreover, immunoprecipitation confirmed that SDF‐1/CXCR4 combined to initiate neurodamage effects.
This study indicated that inhibition of SDF‐1/CXCR4 complex formation can rescue the inflammatory response and alleviate neurobehavioral dysfunction after ICH. SDF‐1/CXCR4 may have applications as a therapeutic target after ICH.