Expression of Aquaporin-1 and Aquaporin-5 in a Rat Model of High-Altitude Pulmonary Edema and the Effect of Hyperbaric Oxygen Exposure.

OBJECTIVE: To investigate the therapeutic roles of hyperbaric oxygen exposure on high-altitude pulmonary edema and to determine whether aquaporin-1 and aquaporin-5 were involved in the pathogenesis of HAPE in rats. METHODS: Rats were divided into 5 groups: The control group, the HAPE group (HAPE model), the HBO group (hyperbaric oxygen exposure), the NBO group (normobaric oxygen exposure), and the NA group (normal air exposure). Western blot and real-time PCR were used to analyze the pulmonary expressions of AQP1 and AQP5. The wet-to-dry (W/D) weight ratio and the morphology of the lung were also examined. RESULTS: The lung W/D weight ratio in the HAPE group was increased compared with the control group. The injury score in the HBO group was noticeably lower than that in the control group. The mRNA and proteins expressions of AQP1 and AQP5 were significantly downregulated in the HAPE group. CONCLUSIONS: Oxygen exposure alleviated high-altitude hypobaric hypoxia-induced lung injury in rats. Additionally, HBO therapy had significant advantage on interstitial HAPE.

Effect of hyperbaric oxygen therapy on HMGB1/NF-κB expression and prognosis of acute spinal cord injury: A randomized clinical trial.

Although there are reports of the beneficial effects of hyperbaric oxygen (HBO) therapy in experimental settings, there are few clinical trials of HBO therapy for acute spinal cord injury (SCI). We investigated the effect of HBO in acute SCI by measuring plasma high mobility group box 1 (HMGB1) and nuclear factor kappa-B (NF-κB) levels, and by monitoring changes in electromyogram F-persistence (the percentage of discernible F-waves) and F-chronodispersion (the difference between minimal and maximal latency). We enrolled 79 acute SCI patients and randomly divided them into control (conventional treatment) and the treatment (conventional treatment plus HBO therapy) groups. Plasma was collected before treatment and after treatment on 1st, 3rd, 7th, 10th and 30th day for the measurement of HMGB1 and NF-κB. Electromyogram F-waves were detected before therapy and after therapy on the 10th and 30th days. Clinical profiles and neurological outcomes were evaluated using American Spinal Injury Association (ASIA) and Frankel Grade scores. Compared to the control group, HBO therapy down-regulated HMGB1 and NF-κB expression in patients with acute SCI on days 3, 7, 10 and 30 (p < 0.05). F-wave chronodispersion decreased at days 10 and 30 (p < 0.01) following HBO. ASIA and Frankel Grade motor/pain scores in the treatment group were significantly improved on day 30 (p < 0.01). There was a positive correlation between plasma NF-κB at day 7 and F-wave dispersion at day 30 (r = 0.76, p = 0.00). In summary, HBO therapy regulated the inflammatory reaction in secondary SCI by decreasing plasma HMGB1/NF-κB levels and reducing the dispersion of electromyogram F-waves of the lower limbs, thereby promoting neurological function recovery.

Evaluation of Hyperbaric Oxygen Treatment in Acute Traumatic Spinal Cord Injury in Rats Using Diffusion Tensor Imaging.

This study aimed to evaluate the therapeutic effect of hyperbaric oxygen (HBO) on acute spinal cord injury (SCI) by measuring the in vivo diffusion tensor imaging (DTI) parameters apparent diffusion coefficient (ADC) and fractional anisotropy (FA) and observing diffusion tensor tractography (DTT) of fiber bundle morphology. The rats were randomly divided into sham-operated (SH), SCI, and SCI and hyperbaric oxygen treatment (SCI + HBO) groups (n = 6 in each group). The Basso-Bettie-Bresnahan (BBB) score was used to evaluate motor function recovery, and DTI was performed on days 3, 7, 14, and 21 after surgery. BBB scores and FA values decreased significantly after SCI, while the two values significantly improved in the SCI + HBO group compared with the SCI group on days 7, 14, and 21. ADC increased significantly on days 14 and 21 postoperatively in the SCI group compared with the SH group but did not significantly differ between the SCI and SCI + HBO groups at any time point. BBB scores had the same variation trend with ADC values and FA values in all three groups. In the SH group, DTT showed a well-organized spinal cord, but the spinal cord showed interruptions at sites of injury after SCI. In conclusion, HBO promotes the recovery of neuronal function after SCI. Parameters of DTI, especially FA, can quantitatively evaluate the efficacy of HBO treatment in SCI, while DTT enables the visualization of the fiber tracking of spinal cord tracts.

Effects of hyperbaric oxygen therapy on RAGE and MCP-1 expression in rats with spinal cord injury.

The inflammatory response is an important source of secondary damage to neuronal tissue in the spinal cord following spinal cord injury (SCI). Hyperbaric oxygen (HBO) therapy reduces inflammation and promotes the restoration of locomotor function following SCI, however, the mechanisms underlying this effect remain to be determined. The aim of the current study was to investigate the mechanisms by which HBO therapy promotes recovery in a rat model of SCI by measuring expression levels of receptor for advanced glycation end products (RAGE) and monocyte chemoattractant protein­1 (MCP­1) in spinal cord tissue. Experimental animals (n=90) were divided into three groups: Sham­operated (SH), SCI (T­10 laminectomy) and SCI + HBO. Each group was further divided into five subgroups (n=6) that were examined at 12 h, and at 1, 3, 7 and 14 days post­injury. Recovery of locomotor function was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring system. Neutrophil infiltration was analyzed using myeloperoxidase (MPO) activity assays. The expression of RAGE and MCP­1 was measured by immunohistochemistry, reverse transcription­quantitative polymerase chain reaction and western blotting. RAGE and MCP­1 expression and MPO activity were higher in the SCI groups than in the SH groups at each time point. HBO therapy reduced RAGE and MCP­1 expression and MPO activity compared with untreated, injured animals at early post­injury stages. In addition, HBO therapy improved BBB scores at post­operative day 7 and 14. HBO therapy was, therefore, demonstrated to relieve secondary inflammatory responses, potentially by inhibiting the expression of RAGE and MCP­1, resulting in significant recovery of locomotor function. The results of the present study may, therefore, be useful in improving the clinical application of HBO therapy for patients with SCI.

Hyperbaric oxygen intervention reduces secondary spinal cord injury in rats via regulation of HMGB1/TLR4/NF-κB signaling pathway.

BACKGROUND: To investigate whether hyperbaric oxygen (HBO) intervention affects the expressions of inflammatory cytokines, HMGB1/TLR4/NF-κB, and arrests secondary spinal cord injury (SCI). METHODS: One hundred and twenty healthy adult SD rats were randomly divided into four groups: sham, sham + HBO, SCI, and SCI + HBO. Each group was then randomly divided into five subgroups of 6 rats each according to the following time points: 1, 2, 3, 7, and 14 d post injury. Functional recovery of the hindlimb was assessed by Basso, Beattie, and Bresnahan (BBB) scores at different time points after SCI. The expression of HMGB1, TLR4, and NF-κB in the spinal cord tissue was determined by fluorescence quantitative PCR, western blot, immunohistochemistry, and ELISA. RESULTS: The gene expressions of TLR4, HMGB1, and NF-κB (P < 0.01) and the TLR4 protein expression were significantly high after SCI. HBO intervention significantly decreased all the four parameters at 3, 7, and 14 d post injury (P < 0.05). A significant positive correlation (P < 0.01) was observed between the following: HMGB1 mRNA, TLR4 mRNA and TLR4 protein; HMGB1 mRNA and NF-κB mRNA; and TLR4 protein and NF-κB mRNA. BBB score was negatively correlated with HMGB1, TLR4 protein and NF-κB levels. HBO intervention significantly improved the BBB scores at 7 and 14 d post injury (P < 0.05). CONCLUSIONS: Hyperbaric oxygen reduced the expressions of HMGB1, TLR4, and NF-κB and reduced secondary SCI as measured using BBB scores.

Effects of hyperbaric oxygen therapy on NACHT domain-leucine-rich-repeat- and pyrin domain-containing protein 3 inflammasome expression in rats following spinal cord injury.

The clinical application of hyperbaric oxygen therapy (HBOT) in spinal cord injury (SCI) has been reported, however the mechanism underlying its therapeutic effects remains to be elucidated. In the present study, SCI was modeled in male Sprague­Dawley rats. A total of 120 rats were randomly divided into four groups: Sham­operated group (SH); sham­operated and hyperbaric oxygen group (SH+HBO); spinal cord injury group (SCI) and spinal cord injury and hyperbaric oxygen treatment group (SCI+HBO). The rats in each group were randomly divided into five smaller groups (12 h, 1, 3, 7 and 14 days after surgery). The mRNA and protein expression levels of NACHT domain­, leucine­rich­repeat­ and pyrin domain­containing protein 3 (NALP3) inflammasome, including NALP3, adaptor molecule apoptosis­associated speck­like protein (ASC) and caspase­1 were determined at several time points following injury. The results of the present study demonstrated that HBOT compromised the mRNA and protein expression levels of NALP3, ASC and caspase­1 in the SCI model rats and HBOT mitigated SCI­induced interleukin 1ß release in the injured spinal cord tissue. It was concluded that HBOT is an effective approach, which can prevent against spinal cord injury, likely by inactivating NALP3 inflammasome.

Hyperbaric oxygen preconditioning promotes neovascularization of transplanted skin flaps in rats.

To determine whether Hyperbaric oxygen preconditioning (HBO-PC) promotes neovascularization by increasing Stromal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in transplanted skin flaps of rats. The epigastric pedicle skin flap was established in a rat model. Rats were randomly assigned to the following five groups: 1) sham-operated group (SH); 2) ischemia followed by reperfusion 3 days postoperatively group (IR3d); 3) ischemia followed by reperfusion 5 days postoperatively group (IR5d); 4) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 3 days postoperatively group (HBO-PC3d); and 5) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 5 days postoperatively group(HBO-PC5d). For the groups receiving HBO-PC, animals underwent 1 hour of HBO at 2.0 ATA in 100% O2 twice per day for 3 days consecutively prior to surgery. After perfusion, Laser Doppler perfusion imaging (LDPI) was performed, and skin flap tissue samples were harvested for histological evaluation and western blot analysis. Perfusion was significantly improved in the HBO-PC groups compared with the IR groups on postoperative 3 and 5. Microvessel density (MVD) was significantly increased by HBO-PC compared with IR groups postoperatively. Western blot analysis revealed that SDF-1 and CXCR4 expression in the HBO-PC groups was significantly increased compared with IR groups. HBO-PC promoted neovascularization via increasing expression levels of SDF-1 and CXCR4 in transplanted skin flaps of rats.

Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury.

Hyperbaric oxygen (HBO) therapy is an effective therapy for ischemia/reperfusion (I/R) injury of the brain, small intestine, testes and liver. However, the detailed molecular mechanisms underlying the effect of HBO therapy remain undetermined. In the current study, the hypothesis that preconditioning rats with HBO protects grafted skin flaps against subsequent I/R injury was investigated. In addition, the molecular mechanisms underlying HBO therapy were characterized by analyzing the roles of the following important inflammatory factors: High mobility group protein 1 (HMGB1) and nuclear factor-κ B (NF-κB). A total of 40 rats were randomly divided into the following five groups: (i) Sham surgery (SH); (ii) ischemia followed by reperfusion 3 days following surgery (I/R3d); (iii) ischemia followed by reperfusion 5 days following surgery (I/R5d); (iv) HBO preconditioning (HBO-PC) and ischemia followed by reperfusion 3 days following surgery (HBO-PC+3d); and (v) HBO-PC and ischemia followed by reperfusion 5 days following surgery (HBO-PC+5d). For the surgical procedure, all pedicled skin flaps were first measured and elevated (9x6 cm). The feeding vessels of the skin flaps were subsequently clamped for 3 h and released to restore blood flow. The rats in the HBO-PC+3d and HBO-PC+5d groups received 1 h HBO for 3 and 5 consecutive days, respectively, prior to surgery. Following surgery, the rats were euthanized, and grafted tissues were collected for western blotting and immunohistochemistry. HBO-PC increased blood perfusion in epigastric skin flaps and attenuated I/R injury following skin flap graft. Additionally, the elevated expression of HMGB1 and NF-κB proteins during I/R injury was attenuated by HBO-PC treatment. HBO-PC may therefore be applied to reduce I/R injury and improve the survival rate of grafted skin flaps. The molecular mechanisms underlying the effect of HBO therapy are associated with the attenuation of inflammatory responses.

Effect of VEGF and CX43 on the promotion of neurological recovery by hyperbaric oxygen treatment in spinal cord-injured rats.

BACKGROUND CONTEXT: Spinal cord injury (SCI) is a serious health issue that may result in high health care costs, with additional social and psychological burdens. Hyperbaric oxygen (HBO) treatment has been found to be beneficial for neurological recovery; however, the underlying mechanisms are yet to be characterized. PURPOSE: The aim of this study was to investigate the mechanisms of HBO treatment in SCI by measuring the expression levels of vascular endothelial growth factor (VEGF) and Connexin43 (CX43) in the injured spinal cord tissue. STUDY DESIGN/SETTING: An experiment animal study of rats undergoing SCI and HBO treatment. METHODS: The spinal cord injury model was established in rats, which were randomly divided into the following four groups: (1) the sham-operated group (SH), (2) the sham-operated and hyperbaric oxygen treatment group (SH+HBO), (3) the spinal cord injury group (SCI), and (4) the spinal cord injury and hyperbaric oxygen treatment group (SCI+HBO). For groups of SH+HBO and SCI+HBO, the animals received 1 hour of HBO at 2.0 ATA in 100% O2 twice per day for 3 days and then daily for the following days consecutively after surgery. After operation, neurological assessments were performed, the spinal cord tissue samples were harvested for histopathological evaluation, Western blot and real-time polymerase chain reaction analysis. RESULTS: The Basso-Bettie-Bresnahan scores were significantly improved in the SCI+HBO group compared with the SCI group on the postoperative 7th and 14th days. The histology scores were significantly decreased by HBO treatment compared with that in the SCI group on the postoperative 3rd, 7th, and 14th days. Western blot analysis and real-time polymerase chain reaction revealed that the expression level of vascular endothelial growth factor (VEGF) in the SCI+HBO group was significantly increased compared with the SCI group. The protein expression level of CX43 and its mRNA level in the SCI+HBO group were significantly decreased on the postoperative 3rd and 7th days, whereas its expression was significantly increased by HBO treatment on the postoperative 14th day compared with the SCI group. CONCLUSIONS: HBO treatment improved neurological recovery when applied after SCI. The expression level changes of VEGF and CX43 may contribute to the further understanding on the molecular mechanisms of HBO treatment on SCI.

Hyperbaric oxygen therapy reduces apoptosis after spinal cord injury in rats.

Hyperbaric oxygen therapy (HBOT) protects brain tissue from inflammatory injury by suppressing mitochondrial apoptotic pathways. However, its neuroprotective mechanism via anti-apoptosis in spinal cord injury (SCI) is still unclear. In our study, Male Sprague-Dawley rats were randomly divided into three groups: sham-operated (SH), SCI model, and SCI + HBOT. Rats in each group were randomly divided into four sub-groups in a time-dependent manner (1 day, 3 days, 7 days and 14 days after surgery). Expression of adaptor molecule apoptosis-associated speck-like protein (ASC) and caspase-3 was evaluated at the indicated time after injury. Our data showed that HBOT downregulated expression of ASC in SCI rats at the mRNA and protein levels. HBOT mitigated caspase-3 release in injured spinal cord tissue. We conclude that HBOT prevents inflammation apoptosis after SCI, likely through suppression of ASC and caspase-3.

Hyperbaric oxygen alleviates experimental (spinal cord) injury by downregulating HMGB1/NF-κB expression.

STUDY DESIGN: We presented an insight into the effect of hyperbaric oxygen (HBO) on spinal cord injury (SCI), aiming to uncover the dynamics of high-mobility group protein B1 (HMGB1) and nuclear factor κB (NF-κB) after HBO intervention in rats with acute SCI. OBJECTIVE: Prognosis of SCI is directly linked with the control of secondary injury, in which the inflammatory response plays a leading role. HBO therapy can reduce this secondary damage to the spinal cord. We used an animal model to characterize the therapeutic effect of HBO on SCI. SUMMARY OF BACKGROUND DATA: A growing number of studies have confirmed that HBO has gradually become an indispensable element after SCI in reducing neurological disorders, and improving the physical function and quality of life of patients. The role of HBO in the process of HMGB1/NF-κB-related secondary inflammatory responses in SCI has yet to be characterized. METHODS: Rats were randomly categorized into sham, sham + HBO, SCI, and SCI + HBO groups. The expression levels of HMGB1 and NF-κB were measured at days 1, 3, 7, and 14 after SCI. RESULTS: After SCI, significant increases in mRNA and protein expression were observed for both HMGB1 and NF-κB (P< 0.01) compared with sham group. HMGB1 mRNA and protein expression levels were decreased after HBO intervention. The decreases were significant at days 7 and 14 (P< 0.05) post-HBO. In the SCI + HBO group, the significant decreases in NF-κB mRNA and protein expression levels were also observed at days 3, 7, and 14 (P< 0.05). After HBO intervention, a significant increase was seen in the Basso, Beattie, and Bresnahan score at days 7 and 14 (P< 0.05). CONCLUSION: HBO intervention may reduce the secondary damage of SCI caused by inflammatory responses via downregulating the expression of HMGB1/NF-κB, and promoting the repair of neurological function. LEVEL OF EVIDENCE: N/A.

Hyperbaric oxygen intervention on expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in spinal cord injury models in rats.

BACKGROUND: Hyperbaric oxygen (HBO) intervention is a main therapeutic method and the curative effect has been certified for spinal cord injury (SCI), but the mechanisms of the neuroprotective effect of HBO on SCI remain elusive. This study aimed to observe the change in expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) after SCI at different time points and to investigate the neuroprotective mechanism of HBO on SCI in rats. METHODS: A total of 160 adult Sprague-Dawley rats, weighing between 250 and 300 g, were randomly assigned to four experimental groups (n = 40 per group). SCI group: SCI was created with a special NYU impactor of Allen's by a 25 gramcentimeter impacting energy on T10 of the spinal cord. SCI+HBO group: HBO therapy after SCI model was established. Sham operation (SH) group: only laminectomy of T10 and no impact on the spinal cord was done. SH+HBO group: HBO therapy after sham operation. The hindlimb functional recovery was evaluated using Basso, Beattie, and Bresnahan (BBB) score and the expressions of HIF-1α and VEGF were observed with fluorescent quantitation PCR and Western blotting method of six rats picked randomly from each group at different time points of 1, 3, 7, and 14 days after operation. RESULTS: Rats in the SCI group and SCI+HBO group were paralyzed completely after operation with BBB 0-1 score. Rats in the SH group and SH+HBO group could walk after sham operation with BBB 20-21 score. The BBB score of rats in the SCI+HBO group (4.67±1.97 and 10.83±2.23) was higher than that in the SCI group (1.83±0.75 and 6.67±2.16) at 7 and 14 days time points obviously (P < 0.05). The expressions of HIF-1a and VEGF in the SCI group and SCI+HBO group were higher than in the SH group and SH+HBO group at any time point obviously (P < 0.05), while the SCI+HBO group presented the least expression of HIF-1α mRNA and protein (3.82±0.41 and 0.59±0.06; 2.26±0.41 and 0.37±0.05; 1.58±0.26 and 0.29±0.05) than that in the SCI group (6.36±0.58 and 0.76±0.07; 3.55±0.47 and 0.51±0.07; 2.27±0.39 and 0.40±0.06) respectively at 3, 7, and 14 days time points (P < 0.05) with significant difference and more expression of VEGF mRNA and protein (5.83±0.77 and 0.72±0.06; 4.59±0.51 and 0.63±0.06) than that in the SCI group (3.06±0.30 and 0.48±0.07; 2.25±0.24 and 0.39±0.09) respectively at 7 and 14 days time points (P < 0.05) with significant difference. CONCLUSIONS: HBO could improve the hind limb functional recovery after SCI in rats. The elevation and duration of the expression of VEGF and the reduction of expression of HIF-1α by HBO intervention may be inversely related in the repair of damaged spinal cord and neuroprotective effect.

Effects of hyperbaric oxygen preconditioning on ischemia-reperfusion inflammation and skin flap survival.

BACKGROUND: Hyperbaric oxygen preconditioning (HBO) is a new method of ischemia preconditioning. In this study, we examined its effects on skin flap survival and the mechanisms involved. METHODS: Thirty-six rats were divided into three groups: HBO preconditioning, control, and sham groups. An extended epigastric adipocutaneous flap based on the right superficial epigastric artery and vein was raised. A 3-hour period of flap ischemia was induced by clamping the pedicle vessels with a microvascular clamp. At the end of ischemia induction, the clamp was removed and the flap was resutured. Rats in the HBO preconditioning group were treated with HBO four times before surgery. Microcirculation in the skin flap was measured on postoperative days 1, 3 and 5. The size of the flap was measured on postoperative day 5, before the animals were sacrificed. Samples of the skin flap were prepared and stained with hematoxylin and eosin. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in the flap samples were measured. RESULTS: Surviving flap size was significantly higher in the HBO preconditioning group compared with controls, with a reduced inflammatory response and increased perfusion. IL-1, TNF-α, and IL-6 levels in the HBO preconditioning group were lower than in controls. CONCLUSIONS: HBO preconditioning improved flap survival in this ischemia-reperfusion rat model. The mechanisms responsible for this effect may relate to attenuation of the inflammatory response and increased flap perfusion following HBO preconditioning.

Effects of stromal cell derived factor-1 and CXCR4 on the promotion of neovascularization by hyperbaric oxygen treatment in skin flaps.

Hyperbaric oxygen (HBO) is known to increase the survival of skin flaps by promoting neovascularization; however, the detailed mechanisms involved are not fully understood. In the present study, we aimed to characterize the effects of HBO treatment on neovascularization and skin flap survival. We also analyzed the mechanisms associated with the expression of angiogenic molecules, such as stromal cell derived factor-1 (SDF­1) and its specific receptor CXCR4, to assess the effects of SDF-1 and CXCR4 on the promotion of neovascularization by HBO treatment in skin flaps. The epigastric pedicle skin flap model was established in rats that were randomly divided into the following groups: i) sham­operated (SH group); ii) ischemia followed by reperfusion and analysis on the third and fifth day (IR3d and IR5d groups, respectively) postoperatively; iii) ischemia followed by reperfusion, HBO treatment and analysis on the third and fifth day (HBO3d and HBO5d groups, respectively) postoperatively. In the two HBO groups, animals received 1 h of HBO treatment in a 2.0 ATA chamber with 100% O2 twice per day for 3 days and then daily for 2 consecutive days following surgery. On the postoperative third and fifth day, skin flap survival measurement, histological analysis, immunohistochemical staining and western blotting for SDF­1 and CXCR4 expression, were performed. Compared with those of the IR groups, skin flap survival, microvessel density (MVD) and expression of SDF­1 and CXCR4 proteins were significantly increased in the HBO groups. Pearson's correlation analysis demonstrated a positive correlation between MVD and the high expression of SDF­1 and CXCR4 following HBO treatment. Results of this study suggested that the effects of HBO treatment in promoting neovascularization may be explained by the upregulation of SDF­1 and CXCR4 expression in the skin flaps of rats.

Diffusion tensor imaging for predicting the clinical outcome of delayed encephalopathy of acute carbon monoxide poisoning.

OBJECTIVE: The aim of the present study was to determine the relationship between neuropsychiatric outcomes and diffusion tensor imaging (DTI) in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). METHODS AND MATERIALS: 66 patients and 60 healthy controls were included in this study. Median fractional anisotropy (FA) of the white matter (WM) bilaterally was compared between patients and healthy controls. The Glasgow Outcome Scale (GOS) was assessed at 4-6 months following DEACMP. The association between the GOS score and FA variables was explored using the Spearman rank correlation. RESULTS: The FA values in WM were reduced in patients with DEACMP compared with those in the volunteers. Of the 66 patients, 21 (31.8%) achieved a good outcome (GOS-5), 26 (36.4%) had moderate disability (GOS-4), 14 (21.2%) had severe disability (GOS-3), 5 (7.6%) were in a vegetative state (GOS-2), and none of the patients died (GOS-1). The FA values in the WM in patients with DEACMP correlated significantly with GOS. CONCLUSION: DTI may be a valuable tool for assessing the severity of brain injury and may be a predictor of outcome in patients with delayed encephalopathy of acute carbon monoxide poisoning. DTI may be a valuable tool for assessing the severity of tissue injury and may be a predictor of outcome.

Effects of hyperbaric oxygen on MMP-2 and MMP-9 expression and spinal cord edema after spinal cord injury.

AIMS: To evaluate the effects of hyperbaric oxygen (HBO) therapy on MMP-2 and MMP-9 expression and spinal cord edema after acute spinal cord injury (SCI). MAIN METHODS: Ninety-six healthy adult Sprague − Dawley rats were randomly divided into 4 groups: sham, sham + HBO, SCI, and SCI + HBO. Each group was subdivided into 4 subgroups of 6 rats each: 24 h, 48 h, 72 h, and 5 d post-injury. The expression levels of matrix metalloproteinase-2 (MMP-2), MMP-9, interleukin (IL-6), and vascular endothelial growth factor (VEGF) were measured using ELISA. The water content of the spinal cord was also measured by Elliot equation. KEY FINDING: MMP-2 and MMP-9 levels and spinal cord water content increased significantly in the SCI group compared to those in the sham and sham + HBO groups at different time points after SCI (P < 0.01). The MMP-2 level was significantly different between the SCI and SCI + HBO groups at 72 h after SCI (P < 0.05), while the MMP-9 level was significantly different at 48 h, 72 h, and 5 d (P < 0.05). The water content of the spinal cord was significantly higher in the SCI group at 5 d after SCI (P < 0. 01). MMP-2 (P < 0.05) and MMP-9 (P < 0.01) levels were positively correlated with spinal cord water content. SIGNIFICANCE: HBO reduced SCI-induced spinal cord edema, stabilized the blood-spinal cord barrier, and promoted recovery of neuronal function by down regulating the expression of IL-6, MMP-2, and MMP-9 and up regulating the expression of VEGF.

The interaction between hepatitis B virus X protein and AIB1 oncogene is required for the activation of NFκB signal transduction.

We identified the interaction between HBV X (HBx) protein and the oncogene AIB1 (amplified in breast cancer 1). A serine/proline motif (SSPSPS) in HBx was found to be required for the interaction. Two LXD motifs [LLXX(X)L, X means any amino acids], LLRNSL and LLDQLHTLL in AIB1 were also found to be involved in the HBx-AIB1 interaction. The HBx-AIB1 interaction was important for the activation of NFκB signal transduction, the HBx mutant that did not interact with AIB1showed dramatically lower NFκB activation activity than the WT HBx. These findings contribute to the new understanding on signal transduction activation mechanisms of HBx.

Investigation of myocardial stunning after cardiopulmonary resuscitation in pigs.

OBJECTIVE: To investigate cardiac function and myocardial perfusion during 48 h after cardiopulmonary resuscitation (CPR), further to test myocardial stunning and seek indicators for long-term survival after CPR. METHODS: After 4 min of untreated ventricular fibrillation, fifteen anesthetized pigs were studied at baseline and 2 h, 4 h, 24 h, and 48 h after restoration of spontaneous circulation (ROSC). Hemodynamic data, echocardiography and gated-single photon emission computed tomography myocardial perfusion images were carried out. RESULTS: Mean arterial pressure (MAP), coronary perfusion pressure (CPP) and cardiac troponin I (CTNI) showed significant differences between eventual survival animals and non-survival animals at 4 h after ROSC (109.2 ± 10.7 mmHg vs. 94.8 ± 12.3 mmHg, P=0.048; 100.8 ± 6.9 mmHg vs. 84.4±12.6 mmHg, P=0.011; 1.60 ± 0.13 ug/L vs. 1.75 ± 0.10 ug/L, P=0.046). Mitral valve early-to-late diastolic peak velocity ratio, mitral valve deceleration time recovered 24 h; ejection faction and the summed rest score recovered 48 h after ROSC. CONCLUSION: Cardiac systolic and early active relaxation dysfunctions were reversible within survival animals; cardiac stunning might be potentially adaptive and protective after CPR. The recovery of MAP, CPP, and CTNI could be the indicators for long-term survival after CPR.

Reducing pulmonary injury by hyperbaric oxygen preconditioning during simulated high altitude exposure in rats.

BACKGROUND: Hyperbaric oxygen preconditioning (HBO2P + HAE) has been found to be beneficial in preventing the occurrence of ischemic damage to brain, spinal cord, heart, and liver in several disease models. In addition, pulmonary inflammation and edema are associated with a marked reduction in the expression levels of both aquaporin (AQP) 1 and AQP5 in the lung. Here, the aims of this study are first to ascertain whether acute lung injury can be induced by simulated high altitude in rats and second to assess whether HBO2P + HAE is able to prevent the occurrence of the proposed high altitude-induced ALI. METHODS: Rats were randomly divided into the following three groups: the normobaric air (NBA; 21% O2 at 1 ATA) group, the HBO2P + high altitude exposure (HAE) group, and the NBA + HAE group. In HBO2P + HAE group, animals received 100% O2 at 2.0 ATA for 1 hour per day, for five consecutive days. In HAE groups, animals were exposed to a simulated HAE of 6,000 m in a hypobaric chamber for 24 hours. Right after being taken out to the ambient, animals were anesthetized generally and killed and thoroughly exsanguinated before their lungs were excised en bloc. The lungs were used for both histologic and molecular evaluation and analysis. RESULTS: In NBA + HAE group, the animals displayed higher scores of alveolar edema, neutrophil infiltration, and hemorrhage compared with those of NBA controls. In contrast, the levels of both AQP1 and AQP5 proteins and mRNA expression in the lung in the NBA + HAE group were significantly lower than those of NBA controls. However, the increased lung injury scores and the decreased levels of both AQP1 and AQP5 proteins and mRNA expression in the lung caused by HAE was significantly reduced by HBO2P + HAE. CONCLUSIONS: Our results suggest that high altitude pulmonary injury may be prevented by HBO2P + HAE in rats.

[The therapeutic effect of small dose of estrogen on cerebral infarction].

OBJECTIVE: To investigate the mechanism of protective effect of estrogen on cerebral damage in ischemic stroke by measuring the estrogen(2) (E(2)), blood lipid, interleukin-1 beta (IL-1 beta), nitric oxide (NO), and also assessment according to national institute of health stroke scale (NIHSS) score, in order to improve the treatment of cerebral infarction. METHODS: Forty male patients, in whom cerebral infarction due to thrombosis of middle cerebral artery was confirmed by CT or magnetic resonance imaging (MRI), were divided into two groups: E(2) therapy (20 cases) and routine therapy (20 cases). Routine therapy was the same in both groups, except 2 mg of E(2) was orally given (2 times a day) to the E(2) therapy group. E(2), testosterone (Ts), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), IL-1 beta, NO, and NIHSS score were measured in each patient at time points of 0, 3, 7, 14 and 21 days. RESULTS: In E(2) group, HDL-C and E(2) were increased significantly, and TC and LDL-C were decreased significantly from 3 days on after treatment, and the changes were obviously more marked than that of routine therapy group (all P<0.05). The changes in TG and Ts were not obvious. NO, IL-1 beta were increased significantly (both P<0.05), and NIHSS score was decreased in routine group form 14 days on after treatment. NO and IL-beta in E(2) group were lower than those in routine therapy group from 3 days on, and the NIHSS score was significantly lower on 14 days and 21 days in E(2) group (both P<0.05). CONCLUSION: The protective effect of E(2) is obvious. It may be due to the results of modulation of blood fat, anti-inflammation and modulation of NO production by the action of E(2). Low dose and short time therapy of E(2) may be beneficial to the patient.