Methane Saline Ameliorates Traumatic Brain Injury through Anti-Inflammatory, Antiapoptotic, and Antioxidative Effects by Activating the Wnt Signalling Pathway
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Published on: April 19, 2024
Meng Li1, Weiman Gao1, Le Ji2
1Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, China.
Objective:
Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved.
Methods:
Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and β-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway.
Results:
Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired.
Conclusion:
Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.
Insights
Methane saline (MS) effectively treats traumatic brain injury (TBI) by reducing inflammation, oxidative stress, and apoptosis. Its therapeutic effects are linked to activating the Wnt signalling pathway, suggesting MS as a potential novel TBI treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Methane saline (MS) exhibits anti-inflammatory, antiapoptotic, and antioxidative properties, beneficial for various diseases.
- The role of MS in treating traumatic brain injury (TBI) and its underlying molecular mechanisms, particularly involving the Wnt signalling pathway, remain unexplored.
Purpose of the Study:
- To investigate the therapeutic effects of MS on TBI in a rat model.
- To determine the optimal dosage of MS for TBI treatment.
- To elucidate the involvement of the Wnt signalling pathway in MS-mediated TBI treatment.
Main Methods:
- Sprague-Dawley rats were subjected to TBI and treated with varying doses of MS (10, 20, 30 ml/kg) or sham.
- Neurological function, histological changes, inflammatory markers, oxidative stress, and apoptosis were assessed.
- The role of the Wnt pathway was examined using a Wnt inhibitor (DKK-1) alongside MS treatment, with molecular markers analyzed via real-time PCR and Western blotting.
Main Results:
- MS significantly reduced inflammation, oxidative stress, and apoptosis in TBI rats, demonstrating neuroprotective effects.
- The optimal therapeutic dose of MS for TBI was determined to be 20 ml/kg.
- Inhibition of the Wnt signalling pathway attenuated the beneficial effects of MS, indicating its crucial role in MS-mediated TBI treatment.
Conclusions:
- Methane saline ameliorates TBI by activating the Wnt signalling pathway, exerting anti-inflammatory, antiapoptotic, and antioxidative effects.
- The Wnt pathway is a significant, though not exclusive, mediator of MS's therapeutic actions in TBI.
- MS represents a promising novel therapeutic strategy for managing traumatic brain injury.
