Abstract
It is well known that hyperbaric oxygen (HBO) therapy achieves neuroprotective effects by modulating neuroinflammatory responses. However, its underlying therapeutic mechanisms are not yet fully elucidated. Based on our previous studies, we further investigated whether HBO therapy exerts neuroprotective effects in vivo by regulating the nuclear factor-kappa B (NF-κB)/ mitogen-activated protein kinases (MAPKs) chemokine (C-X-C motif) ligand (CXCL)1 inflammatory pathway. In our study, a rat model of traumatic brain injury (TBI) was established by controlled cortical impact (CCI) to verify that the expression of CXCL1 and chemokine (C-X-C motif) receptor (CXCR)2 increased after TBI, and CXCL1 was mainly expressed in astrocytes, while CXCR2 was mainly expressed in neurons. Increased apoptosis of cortical nerve cells in the injured cortex was also found after TBI. Reduced nerve cell apoptosis with improved neurological function was observed after application of a CXCR2 antagonist. The expression of phospho-extracellular signal-regulated kinase (p-ERK), phospho-c-Jun N-terminal kinase (p-JNK) and p-NF-κB increased after TBI, and application of ERK, JNK and NF-κB inhibitors decreased expression of CXCL1 and CXCR2 in rats. We further found that HBO therapy down-regulated the expression of p-ERK, p-JNK, p-NF-κB, CXCL1, and CXCR2, and reduced nerve cell apoptosis, improved the neurological function of TBI rats, and ultimately alleviated the secondary injury. In conclusion, HBO therapy may exert neuroprotective effect by regulating the NF-κB/MAPKs (JNK and ERK)-CXCL1 inflammatory pathways following TBI, which probably provide the theoretical and experimental basis for the clinical application of HBO therapy in the treatment of TBI.
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Abbreviations
- TBI:
-
Traumatic brain injury
- CCI:
-
Controlled cortical impact
- HBO:
-
Hyperbaric oxygen
- CXCL:
-
Chemokine (C-X-C motif) ligand
- CXCR:
-
Chemokine (C-X-C motif) receptor
- CCL:
-
Chemokine (C–C motif) ligand
- CCR:
-
Chemokine (C–C motif) receptor
- MAPKs:
-
Mitogen-activated protein kinases
- NF-κB:
-
Nuclear factor-kappa B
- JNK:
-
C-Jun N-terminal kinase
- ERK:
-
Extracellular signal-regulated kinase
- GFAP:
-
Glial fibrillary acidic protein
- IBA-1:
-
Ionized calcium binding adapter molecule 1
- NeuN:
-
Neuronal nuclei
- TUNEL:
-
Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
- DAPI:
-
6-Diamidino-2-phenylindole
- DMSO:
-
Dimethyl sulfoxide
- RT-qPCR:
-
Real-time fluorescence quantitative PCR
- IL:
-
Interleukin
- TNF-α:
-
Tumor necrosis factor-α
- p-:
-
Phospho-
- mNSS:
-
Modified neurological severity scores
- MWM:
-
Morris water maze
- PBS:
-
Phosphate buffer saline
- BSA:
-
Bovine serum albumin
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Acknowledgements
We thank the staff members of our team for their cooperation in this work.
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This project was funded by National Natural Science Foundation of China (No. 81702223), and Science and Technology Planning Project of Nantong (MS22019006).
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AX, HH, WY, YL, HW, SL performed the experiments. SL conceived and designed the study. YL and HW analyzed the data. All authors read and approved the final manuscript.
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Xia, A., Huang, H., You, W. et al. The neuroprotection of hyperbaric oxygen therapy against traumatic brain injury via NF-κB/MAPKs-CXCL1 signaling pathways. Exp Brain Res 240, 207–220 (2022). https://doi.org/10.1007/s00221-021-06249-8
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DOI: https://doi.org/10.1007/s00221-021-06249-8