Hyperbaric Oxygen Alleviates Secondary Brain Injury After Trauma Through Inhibition of TLR4/NF-κB Signaling Pathway.

BACKGROUND: The aim of this study was to investigate the efficacy of hyperbaric oxygen in secondary brain injury after trauma and its mechanism in a rat model. MATERIAL/METHODS: A rat model of TBI was constructed using the modified Feeney's free-fall method, and 60 SD rats were randomly divided into three groups--the sham group, the untreated traumatic brain injury (TBI) group, and the hyperbaric oxygen-treated TBI group. The neurological function of the rats was evaluated 12 and 24 hours after TBI modeling; the expression levels of TLR4, IκB, p65, and cleaved caspase-3 in the peri-trauma cortex were determined by Western blot; levels of TNF-α, IL-6, and IL-1ß were determined by ELISA; and apoptosis of the neurons was evaluated by TUNEL assay 24 hours after TBI modeling. RESULTS: Hyperbaric oxygen therapy significantly inhibited the activation of the TLR4/NF-κB signaling pathway, reduced the expression of cleaved caspase-3, TNF-α, IL-6 and IL-1ß (P<0.05), reduced apoptosis of the neurons and improved the neurological function of the rats (P<0.05). CONCLUSIONS: Hyperbaric oxygen therapy protects the neurons after traumatic injury, possibly through inhibition of the TLR4/NF-κB signaling pathway.

Neuroprotective effects of exogenous methane in a rat model of acute carbon monoxide poisoning.

OBJECTIVE: Delayed neuropsychological sequelae (DNS) are the most common and serious effects of severe carbon monoxide (CO) poisoning, occurring in approximately half of all CO poisoning cases. Growing evidence suggests that oxidative stress and secondary reactions in delayed brain injury are crucial to CO toxicity, similar to ischaemia-reperfusion injury. Exogenous methane plays a protective role in ischaemia-reperfusion injury by affecting key events through anti-oxidant, anti-inflammatory, and anti-apoptosis actions. Our study aimed to explore the potential of exogenous methane to relieve the severity of DNS. METHODS: Thirty-six male Sprague-Dawley (SD) rats were divided into three groups of normal-, CO- and CO plus methane-treated rats. The rats in the latter two groups were exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO exposure, saline or methane saline (10 ml/kg) was intraperitoneally administered to rats in the CO group or the CO plus methane group, respectively. On the ninth day after CO exposure, Morris water maze testing, histological analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and immunohistochemical labelling were performed on 6 rats in each group. The remaining 6 rats in each group were used to detect oxidative damage markers, inflammatory cytokines and apoptosis proteins. RESULTS: Methane significantly improved CO-impaired pathological characteristics as well as learning and memory performance. In addition, methane significantly increased the superoxide dismutase (SOD) activity, lowered the CO-increased level of malondialdehyde (MDA) 3-nitrotyrosine (3-NT) and 8-hydroxy-2-deoxyguanosine (8-OHdG), inhibited levels of tumour necrosis factor-α (TNF-α), interleukin 1-ß (IL1-ß) and caspase-3 in the rat cerebral cortex and hippocampus but had no effect on IL-6 levels. CONCLUSION: The hippocampus was the main target of CO-induced alterations in the rat brain compared to the cerebral cortex. Methane treatment protected the rat brain from the harmful effects induced by CO exposure and improved the outcome of DNS through anti-oxidant, anti-inflammatory and anti-apoptosis activities.

Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and accumulating evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. The aim of this work was to investigate the effect of treatment with hydrogen molecule on the development of disease in mutant SOD1 G93A transgenic mouse model of ALS. Treatment of mutant SOD1 G93A mice with hydrogen-rich saline (HRS, i.p.) significantly delayed disease onset and prolonged survival, and attenuated loss of motor neurons and suppressed microglial and glial activation. Treatment of mutant SOD1 G93A mice with HRS inhibited the release of mitochondrial apoptogenic factors and the subsequent activation of downstream caspase-3. Furthermore, treatment of mutant SOD1 G93A mice with HRS reduced levels of protein carbonyl and 3-nitrotyrosine, and suppressed formation of reactive oxygen species (ROS), peroxynitrite, and malondialdehyde. Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.

Hydrogen-rich saline protects against liver injury in rats with obstructive jaundice.

BACKGROUND: Hydrogen selectively reduces levels of hydroxyl radicals and alleviates acute oxidative stress in many models. Hydrogen-rich saline provides a high concentration of hydrogen that can be easily and safely applied. AIMS: In this study, we investigated the effects of hydrogen-rich saline on the prevention of liver injury induced by obstructive jaundice in rats. METHODS: Male Sprague-Dawley rats (n=56) were divided randomly into four experimental groups: sham operated, bile duct ligation (BDL) plus saline treatment [5 ml/kg, intraperitoneal (i.p.)], BDL plus low-dose hydrogen-rich saline treatment (5 ml/kg, i.p.) and BDL plus high-dose hydrogen-rich saline treatment (10 ml/kg, i.p.). RESULTS: The liver damage was evaluated microscopically 10 days after BDL. Serum alanine aminotransferase and aspartate aminotransferase levels, tissue malondialdehyde content, myeloperoxidase activity, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and high-mobility group box 1 levels were all increased significantly by BDL. Hydrogen-rich saline reduced levels of these markers and relieved morphological liver injury. Additionally, hydrogen-rich saline markedly increased the activities of anti-oxidant enzymes superoxide dismutase and catalase and downregulated extracellular signal-regulated protein kinase (ERK)1/2 activation. CONCLUSIONS: Hydrogen-rich saline attenuates BDL-induced liver damage, possibly by the reduction of inflammation and oxidative stress and the inhibition of the ERK1/2 pathway.

[Diagnosis and therapy of childhood thyroid carcinoma: clinical analysis of 12 cases].

OBJECTIVE: To explore the clinical characteristics, diagnosis and therapy of thyroid carcinoma in children. METHODS: Clinical data of 12 children under the age of 14 years, diagnosed as thyroid carcinoma between August 1998 and August 2008, were reviewed. RESULTS: A hard thyroid mass was observed in 10 out of 12 children with thyroid carcinoma, but only one out of 15 children with benign thyroid tumor (<0.05). The rate of cervical lymph node metastasis in children with thyroid carcinoma was significantly higher than that in children with benign thyroid tumor (<0.05). There was no significant difference in the final diagnostic rate of thyroid carcinoma between ultrasonography and CT scans (75% vs 83%; >0.05). All of 12 cases were pathologically confirmed as differentiated thyroid carcinoma, including papillary carcinoma (7 cases), follicular carcinoma (3 cases) and papillary-follicular carcinoma (2 cases). Nine patients (75%) had cervical lymph node metastasis. All patients received surgical treatment and postoperative thyroxin therapy. No patient was administered with postoperative radioiodine 131I therapy. Unilateral lobectomy plus isthmectomy along with a functional cervical lymph node dissection was a primary operation mode (83%). The follow-up period was 2 months to 10 years. The 5-and 10-year survival rates were 100%. CONCLUSIONS: Childhood thyroid carcinoma is mostly differentiated and characterized by hard thyroid mass and cervical lymph node metastasis. A combination of ultrasonography and CT is helpful to the diagnosis of childhood thyroid carcinoma. The treatment outcome may be satisfactory by optimal therapy in children with thyroid carcinoma.