CNS Neurosci Ther. 2024 Feb;30(2):e14400.doi: 10.1111/cns.14400. Epub 2023 Aug 24.

Stromal cell-derived factor-1 downregulation contributes to neuroprotection mediated by CXC chemokine receptor 4 interactions after intracerebral hemorrhage in rats



  • 1 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Su Zhou, China.
  • 2 Department of Neurosurgery, Linyi People’s Hospital, Linyi, China.
  • 3 Department of Emergency Medicine, The First Affiliated Hospital of Soochow University, Su Zhou, China.


Aim: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: AMD3100; CXC chemokine receptor 4; ICH; neuroprotection; stromal cell-derived factor-1.