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Treatment for traumatic brain injury (TBI) remains elusive despite compelling evidence from animal models for a variety of therapeutic targets. The activation of the NLRP3 (Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome has been proposed as key point in the brain damage associated with TBI. NLRP3 was tested as potential target for reducing neuronal loss and promoting functional recovery in a mouse model of TBI. Male NLRP3 -/- ( n = 20) and wild type ( n = 27) mice were used. A closed TBI model was performed and inflammatory and apoptotic markers were evaluated. A group of WT mice also received BAY 11-7082, a NLRP3 inhibitor, to further evaluate the role of this pathway. At 24 h following TBI NLRP3 -/- animals demonstrated a preserved cognitive function as compared to WT mice, additionally brain damage was less severe and the inflammatory mediators were reduced in brain lysates. The administration of BAY 11-7082 in WT animals subjected to TBI produced overlapping results. At day 7 histology revealed a more conserved brain structure with reduced damage in TBI NLRP3 -/- animals compared to WT. Our data indicate that the NLRP3 pathway might be exploited as molecular target for the short-term sequelae of TBI.

[This corrects the article DOI: 10.3389/fphar.2017.00459.].

The number of out-of-hospital cardiac arrests, cause of disability and death, has dramatically increased worldwide, but despite the progress, the incidence of survival does not appear to have increased significantly. Bystander cardiopulmonary resuscitation (CPR) remains the principal factor in saving out-of-hospital cardiac arrest victims. Analyzing the immense efforts produced by states and professional organizations to train people in CPR skills for immediate intervention in the occurrence of a cardiac arrest, the primary global strategy is centered on CPR education and training for schoolchildren. But the rate of CPR training remains low, with wide differences among communities. The concept of CPR training for schoolchildren to increase bystander CPR rates needs to be implemented. We suggest a global call to action for the tertiary education system for CPR learning and training, including all undergraduate students regardless of the degree course, as a possible method to improve the traditional CPR training today centered on the secondary education system. Extending CPR training courses to the university educational system could significantly increase the number of people educated in life-saving maneuvers. The final objective is to improve the survival rate of patients with out-of-hospital primary cardiac arrest, which has dramatically increased worldwide.

Many of the most common anesthetics are used in surgical oncology, yet effects on cancer cells are still not known. Anesthesia technique could differentially affect cancer recurrence in oncologic patients undergoing surgery, due to immunosuppression, stimulation of angiogenesis, and dissemination of residual cancer cells. Data support the use of intravenous anesthetics, such as propofol anesthesia, thanks to antitumoral protective effects inhibiting cyclooxygenase 2 and prostaglandins E2 in cancer cells, and stimulation of immunity response; a restriction in the use of volatile anesthetics; restriction in the use of opioids as they suppress humoral and cellular immunity, and their chronic use favors angiogenesis and development of metastases; use of locoregional anesthesia compared with general anesthesia, as locoregional appears to reduce cancer recurrence after surgery. However, these findings must be interpreted cautiously as there is no evidence that simple changes in the practice of anesthesia can have a positive impact on postsurgical survival of cancer patients.

The purpose of the study was to determine whether low‐high fidelity medical simulation improves learning and long‐lasting retention of pharmacology knowledge, compared to lecture alone, in undergraduate medical students. Ninety students, before a 45‐minute lecture, were randomized into three groups ‐ sham (S), low (LF), and high fidelity (HF) simulation ‐ to participate in an interactive simulation session. To evaluate immediate and long‐lasting retention, a 20‐item structured questionnaire on inotropic agents was administered to 90 students before and after a 45‐minute lecture, after simulation, and 3 months later. In all groups, the rate of correct answers increased after lecture, while no difference was observed between different groups (P = 0.543). After simulation, students in the HF group provided more correct answers compared to S or LF group (P > 0.001). After 3 months, a significant decrease in the number of correct answers was observed in S (P < 0.001) and LF (P < 0.001) groups, but not in the HF group (P = 0.066). Moreover, HF simulation resulted in an increased number of correct answers compared to the LF (P < 0.001) or S simulation (P < 0.001). These data suggest that advanced medical simulation teaching applied to pharmacology is associated with more effective learning and long‐lasting retention compared to lecture alone.

In designing the anaesthetic plan for patients undergoing surgery, the choice of anaesthetic agent may often appear irrelevant and the best results obtained by the use of a technique or a drug with which the anaesthesia care provider is familiar. Nevertheless, in those surgical procedures (cardiopulmonary bypass, carotid surgery and cerebral aneurysm surgery) and clinical situations (subarachnoid haemorrhage, stroke, brain trauma and post-cardiac arrest resuscitation) where protecting the CNS is a priority, the choice of anaesthetic drug assumes a fundamental role. Treating patients with a neuroprotective agent may be a consideration in improving overall neurological outcome. Therefore, a clear understanding of the relative degree of protection provided by various agents becomes essential in deciding on the most appropriate anaesthetic treatment geared to these objectives. This article surveys the current literature on the effects of the most commonly used anaesthetic drugs (volatile and gaseous inhalation, and intravenous agents) with regard to their role in neuroprotection. A systematic search was performed in the MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINHAL®) and Cochrane Library databases using the following keywords: ‘brain’ (with the limits ‘newborn’ or ‘infant’ or ‘child’ or ‘neonate’ or ‘neonatal’ or ‘animals’) AND ‘neurodegeneration’ or ‘apoptosis’ or ‘toxicity’ or ‘neuroprotection’ in combination with individual drug names (‘halothane’, ‘isoflurane’, ‘desflurane’, ‘sevoflurane’, ‘nitrous oxide’, ‘xenon’, ‘barbiturates’, ‘thiopental’, ‘propofol’, ‘ketamine’). Over 600 abstracts for articles published from January 1980 to April 2010, including studies in animals, humans and in vitro , were examined, but just over 100 of them were considered and reviewed for quality. Taken as a whole, the available data appear to indicate that anaesthetic drugs such as barbiturates, propofol, xenon and most volatile anaesthetics (halothane, isoflurane, desflurane, sevoflurane) show neuroprotective effects that protect cerebral tissue from adverse events — such as apoptosis, degeneration, inflammation and energy failure — caused by chronic neurodegenerative diseases, ischaemia, stroke or nervous system trauma. Nevertheless, in several studies, the administration of gaseous, volatile and intravenous anaesthetics (especially isoflurane and ketamine) was also associated with dose-dependent and exposure time-dependent neurodegenerative effects in the developing animal brain. At present, available experimental data do not support the selection of any one anaesthetic agent over the others. Furthermore, the relative benefit of one anaesthetic versus another, with regard to neuroprotective potential, is unlikely to form a rational basis for choice. Each drug has some undesirable adverse effects that, together with the patient’s medical and surgical history, appear to be decisive in choosing the most suitable anaesthetic agent for a specific situation. Moreover, it is important to highlight that many of the studies in the literature have been conducted in animals or in vitro ; hence, results and conclusions of most of them may not be directly applied to the clinical setting. For these reasons, and given the serious implications for public health, we believe that further investigation — geared mainly to clarifying the complex interactions between anaesthetic drug actions and specific mechanisms involved in brain injury, within a setting as close as possible to the clinical situation — is imperative.

Glutathione (GSH) is a master antioxidant that counters oxidative stress. Clinical studies have confirmed significant depletion of GSH in the hippocampus and the substantia nigra as an early diagnostic biomarker for Alzheimer’s disease (AD) and Parkinson disease (PD), respectively. External agents like anesthetics (inhaled and intravenous) have a different impact on GSH. There is significant depletion of the serum GSH peroxidase level after surgery with isoflurane anesthesia that is not found in patients administered intravenous propofol. The objective of this study is to evaluate the GSH level associated with isoflurane in vitro phantom model using non-invasive magnetic resonance (MR) spectroscopy and to detect residual isoflurane in a solution. MRS data was generated utilizing a 3T MR scanner (Prisma, Siemens) equipped with a 64-channel 1 H head coil and dual tune ( 19 F/ 1 H) head coil. The GSH data acquisition was performed using the MEGA-PRESS pulse sequence using experimental parameters: ON = 4.40 ppm, OFF = 5.00 ppm, TE = 120 ms, TR = 2500 ms, voxel size = 25 × 25 × 25 mm and average = 32. Isoflurane was detected using 19 F MRS studies using 19 F/ 1 H head coil. GSH data was processed using KALPANA package and 19 F data was processed using Siemens package. The GSH peak area (without isoflurane) in a phosphate-buffered solution (PBS) solution (control) showed a slow decline over time due to natural oxidation of GSH to dimeric glutathione (GSSG). On the contrary, the GSH peak area in similar model is reduced significantly ( p  = 0.016) due to isoflurane induced oxidation of GSH to GSSG compared to control. We also report a concise general method for data generation and processing of 1 H MRS data for GSH as well as 19 F monitoring platform using 19 F MR spectroscopy. This is the first report wherein both 1 H and 19 F spectroscopy are applied to generate MRS data along with a unique data processing method. This method is highly sensitive and specifically detects GSH without ambiguity as well as isoflurane due to the unique chemical shift patterns of CF 3 and CHF 2 moieties. This non-invasive MRS approach is developed to monitor GSH-isoflurane interaction leading to oxidative stress and this approach can be extended for other inhaled anesthetics. This methodology using non-invasive 19 F MR spectroscopy needs further development for future clinical studies. Graphical Abstract

Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent that is widely used in adults and children for sedation and the induction and maintenance of anaesthesia. Propofol has gained popularity for its rapid onset and rapid recovery even after prolonged use, and for the neuroprotection conferred. However, a review of the literature reveals multiple instances in which prolonged propofol administration (>48 hours) at high doses (>4 mg/kg/h) may cause a rare, but frequently fatal complication known as propofol infusion syndrome (PRIS). PRIS is characterized by metabolic acidosis, rhabdomyolysis of both skeletal and cardiac muscle, arrhythmias (bradycardia, atrial fibrillation, ventricular and supraventricular tachycardia, bundle branch block and asystole), myocardial failure, renal failure, hepatomegaly and death. PRIS has been described as an ‘all or none’ syndrome with sudden onset and probable death. The literature does not provide evidence of degrees of symptoms, nor of mildness or severity of signs in the clinical course of the syndrome. Recently, a fatal case of PRIS at a low infusion rate (1.9–2.6 mg/kg/h) has been reported. Common laboratory and instrumental findings in PRIS are myoglobinuria, downsloping ST-segment elevation, an increase in plasma creatine kinase, troponin I, potassium, creatinine, azotaemia, malonylcarnitine and C5-acylcarnitine, whereas in the mitochondrial respiratory electron transport chain, the activity of complex IV and cytochrome oxidase ratio is reduced. Propofol should be used with caution for sedation in critically ill children and adults, as well as for longterm anesthesia in otherwise healthy patients, and doses exceeding 4–5 mg/kg/h for long periods (>48 h) should be avoided. If PRIS is suspected, propofol must be stopped immediately and cardiocirculatory stabilization and correction of metabolic acidosis initiated. So, PRIS must be kept in mind as a rare, but highly lethal, complication of propofol use, not necessarily confined to its prolonged use. Furthermore, the safe dosage of propofol may need re-evaluation, and new studies are needed.

Background. The aims of this study were to evaluate the complications that occur after trauma and the characteristics of individuals who develop complications, to identify potential risk factors that increase their incidence, and finally to investigate the relationship between complications and mortality. Methods. We did a population-based retrospective study of trauma patients admitted to ICUs of a level I trauma center. Logistic regression analyses were performed to determine independent predictors for complications. Results. Of the 11,064 patients studied, 3,451 trauma patients developed complications (31.2%). Complications occurred significantly more in younger male patients. Length of stay was correlated with the number of complications (R=0.435,P<0.0001). The overall death rate did not differ between patients with or without complications. The adjusted odds ratio (OR) of developing complication for patients over age 75 versus young adults was 0.7 (P<0.0001). Among males, traumatic central nervous system (CNS) injury was an important predictor for complications (adjusted OR 1.24). Conclusions. Complications after trauma were found to be associated with age, gender, and traumatic CNS injury. Although these are not modifiable factors, they may identify subjects at high risk for the development of complications, allowing for preemptive strategies for prevention.