Abstract
Background
It is well known that hyperbaric oxygen (HBO) therapy achieves neuroprotective effects by suppressing or relieving 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 NF-κB/ MAPKs-CXCL1 inflammatory pathway.
Methods
A rat model of traumatic brain injury (TBI) was established by controlled cortical impact (CCI). The cellular distribution of CXCL1 and CXCR2 was observed by double immunofluorescence labeling. The neurological function of TBI rats was assessed by modified neurological severity scores and Morris water maze methods. TUNEL staining was performed to observe apoptosis of neuronal cells in the injured cortical area. The changes in neural function, neuronal apoptosis, and expression of CXCL1, CXCR2, NF-κB, and MAPKs (ERK and JNK) were observed in TBI rats treated with CXCR2 antagonist, ERK, JNK, and NF-κB inhibitor or HBO therapy.
Results
The expression of CXCL1 and CXCR2 increased after TBI, and cell localization analysis revealed that CXCL1 was mainly expressed in astrocytes, while CXCR2 was mainly expressed in neurons. Increased apoptosis of cortical neurons in the injury area was also found after TBI. Reduced neuronal apoptosis with improved neurological function was observed after application of a CXCR2 antagonist. The expression of p-ERK, 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 neuronal apoptosis, improved the neurological function of TBI rats, and ultimately alleviated the secondary injury.
Conclusions
CXCL1- CXCR2 mediates the interaction of activated astrocytes and neurons, exacerbating secondary injury after TBI. HBO therapy exerts neuroprotective effects by regulating the NF-κB/ MAPKs (JNK and ERK)- CXCL1 inflammatory pathway to control neuroinflammation after TBI, which provides the theoretical and experimental basis for the clinical application of HBO therapy in the treatment of TBI.
Effects of hyperbaric oxygen on the Nrf2 signaling pathway in secondary injury following traumatic brain injury
