Conditional deletion of IkBin hematopoietic cells promotes functional recovery after spinal cord injury in mice

Background: Transcription factor protein IkB (encoded by the Nfkbiz gene) regulates nuclear factor-kB (NF-kB) and is involved in the pathophysiology of various inflammatory diseases. However, the role of IkB in secondary damage following spinal cord injury (SCI) remains to be determined. Here, we investigated the effect of IkB expressed in hematopoietic cells on the progression of secondary damage and functional recovery after SCI. Methods: We used conditional IkB -knockout mice (Mx1-Cre;Nfkbizfl/f) to examine the role of IkB in hematopoietic cells after SCI. Contusion SCI was induced using a force of 60 kdyn. The recovery of locomotor performance was evaluated using the nine-point Basso Mouse Scale (BMS) until 42 days postinjury. Expression patterns of inflammatory cytokines and chemokines were examined by quantitative real-time PCR or proteome array analysis. Bone marrow transplantation (BMT) was performed to eliminate the effect of IkB deletion in non-hematopoietic cells. Results: Mx1-Cre;Nfkbizfl/fl mice had significantly improved locomotor function compared with wild-type (WT) mice. The mRNA expression of Nfkbiz in WT mice peaked at 12 h after SCI and then decreased slowly in both the spinal cord and white blood cells. In situ hybridization showed that Nfkbiz mRNA was localized in cell nuclei, including macrophage-like cells, in the injured spinal cord of WT mice at 1 day after SCI. Compared with WT mice, Mx1-Cre;Nfkbizfl/fl mice had significantly increased mRNA expressions of interleukin (Il)-4 and Il-10 in the injured spinal cord. In addition, Mx1-Cre;Nfkbizfl/fl mice had significantly higher protein levels of granulocyte-macrophage colony-stimulating factor and C-C motif chemokine 11 compared with WT mice. BMT from Mx1-Cre;Nfkbizfl/fl mice into WT mice improved functional recovery after SCI compared with control mice (WT cells into WT mice). Conclusions: IkB deletion in hematopoietic cells improved functional recovery after SCI, possibly by shifting the inflammatory balance towards anti-inflammatory and pro-regenerative directions. (c) 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.