Methane Saline Ameliorates Traumatic Brain Injury through Anti-Inflammatory, Antiapoptotic, and Antioxidative Effects by Activating the Wnt Signalling Pathway

Abstract

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.

Methane-Rich Saline Ameliorates Depressive-Like Behaviors During Chronic Unpredictable Mild Stress (CUMS)

“…Methane has been able to protect the brain against the damage caused by carbon monoxide by reducing in ammatory cytokines and improving antioxidant enzymes [39]. In the brain trauma model, methane, by blocking the pathway of the Wnt, reduced the in ammatory and oxidative responses and inhibited apoptosis, and nally improved the cognitive function of animals [40]. In another study, methane inhalation reduced neurological dysfunction following cerebral ischemia-reperfusion by activating the PI3K/Akt/HO-1-dependent antioxidant pathway [41].…”

A narrative review of methane in treating neurological diseases

“…Li et al[ 18 ] reported that methane exerts protective effects on TBI. Increased neurological severity score, more residual neurons, and higher superoxide dismutase level were observed after TBI, while treatment with MS could improve these indicators.…”

“…In another studies,[ 15 16 ] methane was injected six times within 3 days. In a study by Li et al,[ 18 ] methane was even injected for 7 consecutive days ( Table 1 ).…”

“…Methane exert protective effects on various neurological diseases, such as carbon monoxide (CO) poisoning injury,[ 14 ] spinal cord injury (SCI),[ 15 16 ] cerebral I/R injury,[ 17 ] and traumatic brain injury (TBI). [ 18 ] However, there are a lot of differences in the indicators and administration methods of methane. A review focusing on the administration routes of methane will provide evidence for future research on practical observational indicators, research methods, and even meaningful mechanisms.…”