Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice.

Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1ß (IL-1ß) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1ß levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1ß levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.

Two cases of cryptogenic life-threatening hemoptysis - identification and management of bleeding point.

Cases: Case 1: A 63-year-old woman was referred for coughing blood. Although cardiorespiratory dynamics were stabilized by artificial respiration under sedation, severely poor ventilation developed from asphyxia associated with massive respiratory tract hemorrhage. One-lung ventilation was temporarily secured by endotracheal tube insertion into the left main bronchus just prior to cardiopulmonary arrest.Case 2: A 72-year-old man was referred for massive hemoptysis after coughing, then intubated and placed on a respirator. During angiography, blood clots collected with bronchoscopy confirmed extravascular leakage into the right main bronchus. Outcomes: Both showed no hemoptysis recurrence after bronchial artery embolization and were discharged. Case 1 required intensive treatment for 6 days, including artificial respiratory management. Conclusion: Emergency one-lung ventilation was required for asphyxia in Case 1, and we had difficulties with bleeding point identification and hemostatic therapy. From that experience, we noted hemoptysis during angiography using bronchoscopy in Case 2, enabling prompt bronchial artery embolization.

Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24 h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3 h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6 h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3 h. Histological analysis revealed lung injury at 6 and 24 h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.

The Beneficial Effects of ETS-GS, a Novel Vitamin E Derivative, on a Rat Model of Crush Injury.

Crush syndrome is a devastating condition leading to multiple organ failure. The mechanisms by which local traumatic injuries affect distant organs remain unknown. ETS-GS is a novel water-soluble, stable anti-oxidative agent composed of vitamin E derivative. Given that one of the main pathophysiological effects in crush syndrome is massive ischemia-reperfusion, reactive oxygen species (ROS) generated from the injured extremities would be systemically involved in distant organ damage. We investigated whether ETS-GS could suppress inflammatory response and improve mortality in a rat model of crush injury. Crush injury was induced by compression of bilateral hindlimbs for 6 h followed by release of compression. Seven-day survival was significantly improved by ETS-GS treatment. To estimate anti-oxidative and anti-inflammatory effects of ETS-GS, serum was collected 6 and 20 h after the injury. ETS-GS treatment significantly dampened the up-regulation of malondialdehyde and reduction of superoxide dismutase in the serum, which were induced by crush injury. Serum levels of interleukin 6 and high mobility group box 1 were significantly decreased in the ETS-GS group compared with those in the control group. Lung damage shown by hematoxylin-eosin staining at 20 h after the injury was ameliorated by the treatment. Ex vivo imaging confirmed that ETS-GS treatment reduced ROS generation in both the lung and the muscle following crush injury. The administration of ETS-GS could suppress ROS generation, systemic inflammation, and the subsequent organ damage, thus improving survival in a rat model of crush injury. These findings suggest that ETS-GS can become a novel therapeutic agent against crush injury.

Effect of Histone Acetylation on N-Methyl-D-Aspartate 2B Receptor Subunits and Interleukin-1 Receptors in Association with Nociception-Related Somatosensory Cortex Dysfunction in a Mouse Model of Sepsis.

Whole-body inflammation (i.e., sepsis) often results in brain-related sensory dysfunction. We previously reported that interleukin (IL)-1 resulted in synaptic dysfunction of septic encephalopathy, but the underlying molecular mechanisms remain unknown, as do effective treatments. Using mice, we examined immunohistochemistry, co-immunoprecipitation, enzyme-linked immunosorbent assay, and behavior analyses, and investigated the role of the N-methyl-D-aspartate 2B subunit (NR2B) of NMDA receptor, IL-1 receptor, and histone acetylation in the pathophysiology underlying sensory dysfunction induced by lipopolysaccharide (LPS). Mice groups of sham-operated, LPS, LPS with an NR2B antagonist, or LPS with resveratrol (a histone acetylation activator) were analyzed. We found that LPS increased NR2B and interleukin-1 receptor (IL-1R) immunoreactivity. The expression of Iba1, a marker for microglia and/or macrophages, increased more significantly in the brain than in the spinal cord, implicating NR2B and IL-1R in brain inflammation. Immunoprecipitation with NR2B and IL-1R revealed related antibodies. Blood levels of IL-1ß (i.e., the IL-1R ligand) increased, though not significantly, suggesting that inflammation peaked at 20 h. Behavioral assessments of central (CNS) and peripheral sensory (PNS) function indicated that LPS delayed CNS but not PNS escape latency. Finally, NR2B antagonist or resveratrol in the lateral ventricle antagonized the effects of LPS in the brain and improved animal survival. In summary, histone acetylation may control expression of NR2B and IL-1R, alleviating inflammation-induced sensory neuronal dysfunction caused by LPS.

Reduction of thoracic aorta motion artifact with high-pitch 128-slice dual-source computed tomographic angiography: a historical control study.

OBJECTIVES: Electrocardiogram-gated imaging combined with multi-detector row computed tomography (MDCT) has reduced cardiac motion artifacts, but it was not practical in the emergency setting. The purpose of this study was to evaluate the ability of a high-pitch, 128-slice dual-source CT (DSCT) scanner to reduce motion artifacts in patients admitted to the emergency room. METHODS: This study comprised 100 patients suspected of having thoracic aorta lesions. We examined 47 patients with the 128-slice DSCT scanner (DSCT group), and 53 patients were examined with a 64-slice MDCT scanner (MDCT group). Six anatomic areas in the thoracic aorta were evaluated. RESULTS: Computed tomography images in the DSCT group were distinct, and significant differences were observed in images of all areas between the 2 groups except for the descending aorta. CONCLUSIONS: The high-pitch DSCT scanner can reduce motion artifacts of the thoracic aorta and enable radiological diagnosis even in patients with tachycardia and without breath hold.

Electrical vagus nerve stimulation attenuates systemic inflammation and improves survival in a rat heatstroke model.

This study was performed to gain insights into novel therapeutic approaches for the treatment of heatstroke. The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical vagus nerve stimulation (VNS) reportedly suppresses pro-inflammatory cytokine release in several models of inflammatory disease. Here, we evaluated whether electrical VNS attenuates severe heatstroke, which induces a systemic inflammatory response. Anesthetized rats were subjected to heat stress (41.5°C for 30 minutes) with/without electrical VNS. In the VNS-treated group, the cervical vagus nerve was stimulated with constant voltage (10 V, 2 ms, 5 Hz) for 20 minutes immediately after completion of heat stress. Sham-operated animals underwent the same procedure without stimulation under a normothermic condition. Seven-day mortality improved significantly in the VNS-treated group versus control group. Electrical VNS significantly suppressed induction of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in the serum 6 hours after heat stress. Simultaneously, the increase of soluble thrombomodulin and E-selectin following heat stress was also suppressed by VNS treatment, suggesting its protective effect on endothelium. Immunohistochemical analysis using tissue preparations obtained 6 hours after heat stress revealed that VNS treatment attenuated infiltration of inflammatory (CD11b-positive) cells in lung and spleen. Interestingly, most cells with increased CD11b positivity in response to heat stress did not express α7 nicotinic acetylcholine receptor in the spleen. These data indicate that electrical VNS modulated cholinergic anti-inflammatory pathway abnormalities induced by heat stress, and this protective effect was associated with improved mortality. These findings may provide a novel therapeutic strategy to combat severe heatstroke in the critical care setting.

Systemic involvement of high-mobility group box 1 protein and therapeutic effect of anti-high-mobility group box 1 protein antibody in a rat model of crush injury.

Patients with crush injury often present systemic inflammatory response syndrome and fall into multiple organ failure. The mechanism by which the local tissue damage induces distant organ failure is still unclear. We focused on high-mobility group box 1 protein (HMGB1) as one of the damage-associated molecular pattern molecules that cause systemic inflammation in crush injury. We investigated involvement of HMGB1 and the effects of treatment with anti-HMGB1 antibody in a rat model of crush injury. Both hindlimbs of rats were compressed for 6 h and then released. In the crush injury group, the level of serum HMGB1 peaked at 3 h after releasing compression, followed by the increasing in the serum levels of interleukin 6 and tumor necrosis factor α. Hematoxylin-eosin staining showed substantial damage in the lung 24 h after the crush injury, with upregulation of the expression of receptor for advanced glycation end products, as revealed by immunohistochemical analysis. Intravenous administration of anti-HMGB1 antibody improved survival (n = 20 each group) and significantly suppressed serum levels of HMGB1, interleukin 6, and tumor necrosis factor α compared with the untreated crush injury group (n = 6-9 each group). Histological findings of lung damage were ameliorated, and the expression of receptor for advanced glycation end products was hampered by the treatment. These results indicate that HMGB1 is released in response to damage immediately after crush injury and acts as a proinflammatory mediator. Administration of anti-HMGB1 antibody reduced inflammatory reactions and improved survival by blocking extracellular HMGB1. Thus, HMGB1 appears to be a therapeutic target, and anti-HMGB1 antibody may become a promising novel therapy against crush injury to prevent the progression to multiple organ failure.

Blunt tracheal transection repair requiring open abdominal management.

A 19-year-old man sustained multiple injuries during a motorcycle accident. A computed tomographic scan revealed that the trachea was completely transected, and the endotracheal tube did not reach the distal stump. Extracorporeal membrane oxygenation was used to maintain oxygenation and avoid mediastinal emphysema. Tracheal anastomosis through a right thoracotomy was planned initially, but prior to the operation, extracorporeal membrane oxygenation flow and respiratory condition deteriorated, with evidence of oxygen desaturation. An abdominal compartment syndrome was diagnosed, and open abdominal management was performed. Therefore, the patient had to undergo tracheal anastomosis through a median sternotomy in the supine position. The laparotomy was closed, and the patient was discharged without respiratory complications.