Osteoclastic craniectomy for scaphocephaly in infants results in physiological head shapes.

INTRODUCTION: Sagittal synostosis leading to scaphocephaly is the most common type of craniostenosis being operated. Different treatment options are known, but the optimal treatment method is still controversial. Head growth indicated by measurements of the head´s circumference and cephalic index (CI) are valid surrogate parameters for normal head shapes in children. The aim of the study was to analyze if osteoclastic craniectomy (OC) in scaphocephaly children at four to ten months of age results in normal head shapes. PATIENTS AND METHODS: Twenty-seven patients with scaphocephaly underwent OC between 2003 and 2011. The mean patient age at the time of surgery was 6.75 months. The body weight was between 6.1 and 9.3 kg, mean 8.0 kg. The average duration of surgery was 108 minutes. The mean blood loss during the procedure was 168 ml and the mean amount of erythrocyte transfusion was 152 ml. The mean time spent on the ICU was 1.48 days and the mean of total hospital stay was 5.81 days. The operative method is described. During the mean follow-up time of 6.3 years (min 3.8, max 10.4, median 7.1) focus was set on the patient´s head growth and cephalic index (CI) following OC. For statistical reason the follow up period was divided into three groups: follow up 2-4 years, 5-7 years and 8-10 years. RESULTS: For all cases the total head growth was 9.5cm (mean) during the follow up period of 6.3 years. Analyzing the mean head growth by bootstrapping analysis, the three observational groups showed a significant increase of the head circumference in all cases being analyzed: group 1 p=0.003, group 2 p=0.005 and group 3 p=0.028 Evaluation of the CI showed a statistically significant change from a pathologic value of 0.67 (mean) preoperatively to a normal value of 0.78 (mean) postoperatively during the follow up analyzing all patients. To precise these findings, the bootstrapping analysis showed in the first period an increase of the mean CI not reaching statistical significance (p=0.351). Analyzing the second and third period the CI significantly increased in both groups (p=0.016 and p=0.037). All patients showed a nearly complete re-ossification during the follow up period. No secondary operation was necessary in any patient of this cohort. CONCLUSION: As shown in this single-center observational study, the surgical intervention significantly improved the cephalic index and resulted in a symmetric head shape with excellent aesthetic appearance. The results were not dependent on postoperative helmet therapy, and compliance of caregivers. Re-ossification reached 100% within the observation period. According to these data, we recommend osteoclastic craniectomy as the method of choice in infants six to twelve months of age.

[Reduction of treatment time for children in the trauma room care : Impact of implementation of an interdisciplinary trauma room concept (iTRAPS)]. / Verkürzung der Versorgungszeit im Trauma-Schockraum für Kinder : Auswirkungen der Einführung eines interdisziplinären Schockraumkonzepts (iTRAPS).

INTRODUCTION: In addition to infrastructural and conceptual planning, smooth interdisciplinary cooperation is crucial for trauma room care of severely injured children based on time-saving management and a clear set of priorities. The time to computed tomography (CT) is a well-accepted marker for the efficacy of trauma management. Up to now there are no guidelines in the literature for an adapted approach in pediatric trauma room care. METHODS: A step-by-step algorithm for pediatric trauma room care (Interdisciplinary Trauma Room Algorithm in Pediatric Surgery, iTRAPS) was developed within the framework of an interdisciplinary team: pediatric surgeons, pediatric anaethesiologists, pediatric intensivists and pediatric radiologists. In two groups of patients from January 2014 to April 2015 (group 1) and from July 2015 to January 2017 (group 2) process quality was monitored by the time required for trauma room treatment until the CT scan was performed and used as a surrogate marker. Inclusion criteria were patients aged 0-16 years, who were evaluated in a level 1 pediatric trauma room with an injury severity score (ISS) ≥8 and the necessity for a CT scan. RESULTS: Before (group 1) and after (group 2) implementation of iTRAPS 16 patients were included in each group. There were no significant differences between the age and the ISS in the two groups of patients. The required time for trauma room treatment was significantly reduced from an average of 33.6 min before to 15.2 min after implementation of iTRAPS (p < 0.01). DISCUSSION: The required time for the trauma care room treatment could be significantly reduced by more than half after the implementation of iTRAPS. The reasons were the interdisciplinary organization of the trauma room leadership, reorganization of patient transfer and improved briefing by emergency doctors. CONCLUSION: Besides a well-organized trauma team, it is essential that the trauma room workflow is adapted to the specific structure of the hospital. Despite the limitations of the study the data demonstrate that the trauma room workflow enables an efficient management. By the interdisciplinary reorganization of the pediatric trauma room treatment with improved structures and standardized processes, patient care was more effective with a significant reduction in the time required for trauma room treatment. The suggested iTRAPS concept could be used as a framework to establish individualized workflows for pediatric trauma room treatment in other hospitals. This algorithm should be supplemented by standardized operating procedures (SOPs) for the differentiated radiological diagnostic procedures in areas of traumatic brain injury (TBI), thoracic and abdominal trauma in children.

Chronic stress changes prepulse inhibition after amphetamine challenge: the role of the dopaminergic system.

The goal of this research was to examine the influence of chronic mild stress (CMS) on prepulse inhibition (PPI). We used an amphetamine challenge to study the role of the dopaminergic system in limbic structures. Chronic stress caused a reduction in both sucrose preference and body weight. It was found that the initially strong response to amphetamine in the control rats was weakened after stress on both the behavioural and biochemical levels: improved PPI, decreased dopamine D2 receptor expression in the central nucleus of amygdala (CeA) and nucleus accumbens (NAC), and decreased dopamine and 3-MT (3-methoxytyramine) levels in NAC. We observed that the stress-evoked attenuation of amphetamine-induced stimulation was also paralleled by changes in corticosterone level. These effects were accompanied by a decrease in both glutamate and the glutamate/gamma-aminobutric acid (GABA) ratio in the NAC. The interpretation of these results is that prolonged stress induces compensatory mechanisms in the mesolimbic system which are responsible for psychostimulant (amphetamine) effects.

Corticotropin releasing factor receptor 1 antagonist differentially inhibits freezing behavior and changes gamma-aminobutyric acidergic activity in the amygdala in low- and high-anxiety rats.

The aim of this study was to examine the effects of non-peptide corticotropin-releasing factor receptor 1 (CRF1) antagonist (antalarmin) administration on rat conditioned fear responses and gamma-aminobutyric acid (GABA)-ergic brain activity (GAD67 expression and GABA concentration) in low-anxiety (LR) and high-anxiety (HR) rats. The animals were divided into the LR and HR groups based on the duration of their conditioned freezing response in the first contextual fear test. After 28 days, the animals were re-subjected to the contextual fear training and test. The rats received an antalarmin injection (10 mg/kg or 20 mg/kg) 80 min before the second exposure to the aversive context. Antalarmin significantly attenuated the conditioned fear response only in the HR rats. The behavioral effect of a lower dose (10 mg/kg) of antalarmin was accompanied by increased GAD67 expression in the prelimbic cortex (PL) and central nucleus of the amygdala (CeA) and an increased GABA concentration in the amygdala. These studies showed that HR rats were more susceptible to the anxiolytic effects of CRF1 antagonist administration, which were associated with increased GABAergic activity in the medial prefrontal cortex and amygdala. The current data may provide insights into the neurobiological mechanism operating within the mesolimbic CRF-GABA neurotransmitter systems, which may be responsible for individual differences in stress-related diseases. This knowledge can be applied to further elucidate the pathophysiology of anxiety and trauma/stress-related disorders.

Sensitivity and Efficacy of Boscalid, Fluazinam, and Thiophanate-Methyl for White Mold Control in Snap Bean in New York.

White mold (Sclerotinia sclerotiorum) of leguminous crops in New York is generally managed with preventive applications of fungicides. However, no research has been conducted during the last decade to assess the sensitivity of the S. sclerotiorum population to fungicides or compare their performance under field conditions. The sensitivity of S. sclerotiorum to boscalid, fluazinam, and thiophanate-methyl was assessed in 151 isolates from 15 fields across New York using an agar dilution method with discriminatory concentrations. In addition, the effective concentration at which mycelial growth is reduced by 50% (EC50) was estimated for one representative isolate from each field. The efficacy of commercial formulations of each fungicide on white mold incidence in plants and pods was also tested in two field trials (2015 and 2016). The EC50 values ranged from 0.068 to 0.219, 0.001 to 0.002, and 1.23 to 2.15 µg/ml for boscalid, fluazinam, and thiophanate-methyl, respectively. Evidence of resistance was not found using the discriminatory concentration tests. The mycelial growth inhibition relative to the control ranged from 56 to 83%, 66 to 84%, and 53 to 83% at discriminatory concentrations of boscalid (5 µg a.i./ml), fluazinam (0.05 µg a.i./ml), and thiophanate-methyl (5 µg a.i./ml), respectively. Fourteen isolates with mycelial growth inhibition lower than 60% at 5 µg/ml of thiophanate-methyl, did not exhibit point mutations within a partial sequence of the ß-tubulin gene. In the field trials, fungicides effectively reduced white mold incidence on plants by 75% (2015) and 93% (2016) and on pods by 81% (2015) and 87% (2016), both relative to the nontreated plots. However, fungicide applications led to significant increases in pod yield, relative to the nontreated plots, only in 2015 when the incidence of white mold on plants and pods were higher (85 and 49.2%) than in 2016 (31.3 and 10.3%). Although fungicide resistance was not detected, and thus control failures reported by New York snap bean growers may be due to other factors, further monitoring of sensitivity within the S. sclerotiorum population is encouraged as well as the use of rational systems to base their judicious and economic use.

Similar Aggressiveness of Phenotypically and Genotypically Distinct Isolates of Sclerotinia sclerotiorum.

Understanding how Sclerotinia sclerotiorum aggressiveness varies among isolates may be useful for breeding programs aimed at developing common bean cultivars resistant to white mold. The aggressiveness of 20 S. sclerotiorum isolates collected in common bean fields from four Brazilian states was tested against two common bean genotypes (Pérola and A195) using two inoculation methods. The isolates were characterized using 10 microsatellite (SSR) loci, mycelial compatibility groups (MCGs), partial sequences of the oxaloacetate acetylhydrolase (OAH) gene, and morphological traits. Twenty SSR and seven OAH haplotypes, 10 MCGs, and high variability in colony morphology were found. One isolate was more aggressive when inoculated on plants of the genotype A195, but all other isolates had similar aggressiveness. Aggressiveness was not related with MCGs, SSR, OAH haplotypes, mycelial pigmentation, growth rate, or sclerotia production.

[Establishment of a Neonatal ECMO Programme on the Basis of a Special Training Programme--A 6-year Analysis]. / Etablierung neonataler ECMO bei Lungenversagen auf der Grundlage eines speziellen Trainingsprogramms--Eine 6-Jahres-Analyse.

BACKGROUND: Internationally the need for neonatal ECMO is decreasing and the Extracorporeal Life Support Organization (ELSO) recommends that centres providing neonatal ECMO should treat at least 6 children per year. METHOD: After a one-year training programme and preparation of the clinical application, neonatal ECMO was established and subsequently 41 infants [median age 1 day (1-172 days), median weight 3.25 kg (1.27-5.79 kg)] with severe respiratory failure have been treated within a 6-year period (fall 2008-fall 2014). For rescue therapy we provide inhaled nitric oxide, high-frequency oscillation and other differentiated ventilator strategies. Parallel to the clinical use of ECMO all employees have been trained in a special programme at 3-monthly intervals. RESULTS: By establishing an elaborate training programme and concentrating the treatment of critically ill newborns in one centre, the expertise of both running and preventing of neonatal ECMO due to pulmonary failure can be achieved. The diagnoses correlate to those of other centres which perform neonatal ECMO. 13 infants needed ECMO. The resulting overall survival rate was 11/12 (91.7%) infants treated with ECMO with a curative approach. All patients could be weaned from ECMO. CONCLUSION: In the context of a specialised university hospital with all treatment options for critically ill newborns and with the establishment of a specialised training programme, neonatal ECMO for pulmonary failure can achieve equally good results in comparison to those of national and international ECMO centres.

Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation.

Neutrophil infiltration and activation in the lung are important pathophysiological features in COPD, severe asthma and bronchiectasis mostly mediated by CXCL8 and CXCL1 via CXCR1 and CXCR2. No thorough study to date has been performed to compare the anti-inflammatory effect profile of dual CXCR1/2 vs. selective CXCR2 antagonists in relevant human neutrophil assays and pulmonary inflammation models. Dual CXCR1/2 (SCH527123, diaminocyclobutandione-1) and selective CXCR2 (SB265610, thiopyrimidine-1) antagonist activity and receptor residence time were determined by [(35)S]GTPγS binding in human (h)- and guinea pig (gp)-CXCR1 and CXCR2 overexpressing membranes. h-neutrophil chemotaxis, degranulation and ROS production were established using CXCL8 or CXCL1 to evaluate dual CXCR1/2- or selective CXCR2-dependent activities. LPS-induced lung inflammation in gp was selected to assess in vivo potency. Dual CXCR1/2 antagonists blocked both CXCL8 and CXCL1-induced h-neutrophil functions and [(35)S]GTPγS binding. In contrary, selective CXCR2 antagonists displayed significantly reduced potency in CXCL8 -mediated h-neutrophil responses despite being active in CXCR2 assays. Upon LPS challenge in gp, administration of SCH527123 inhibited the increase of neutrophils in BALF, modestly reduced blood neutrophils and induced minor neutrophil accumulation in bone marrow. Differentiation of CXCR1/2 vs. CXCR2 antagonists could not be extended to in vivo due to differences in CXCR1 receptor homology between h and gp. Dual CXCR1/2 therapy may represent a promising anti-inflammatory treatment for respiratory diseases reducing more effectively neutrophil migration and activation in the lung than a CXCR2 selective treatment. However, the in vivo confirmation of this claim is still missing due to species differences in CXCR1.

Potencial de óleos essenciais de plantas medicinais no controle de fitopatógenos / Potential of essential oils from medicinal plants to control plant pathogens

Além do valor como recurso terapêutico, plantas medicinais também possuem potencial para serem utilizadas como fonte de princípios ativos contra fitopatógenos. O objetivo deste trabalho foi avaliar o efeito de óleos essenciais das espécies medicinais Baccharis dracunculifolia (alecrim-do-campo), Schinus terebinthifolius (aroeirinha) e Porophyllum ruderale (arnica-brasileira) sobre o crescimento dos fungos fitopatogênicos Fusarium oxysporum f. sp. phaseoli (Fop), F. solani f. sp. phaseoli (Fsp), Sclerotinia sclerotiorum (Ss), S. minor (Sm), Rhizoctonia solani (Rs), Sclerotium rolfsii (Sr) e Macrophomina phaseolina (Mp). Avaliou-se em placas de Petri o crescimento radial desses fungos em meio batata-dextrose-ágar (BDA) com cinco concentrações (0, 250, 500, 1000 e 3000 mg L-1) dos óleos essenciais. Discos de micélio (5 mm de diâmetro) de cada fungo em crescimento foram transferidos para placas de Petri que foram mantidas a 23°C no escuro por 48 horas. O óleo essencial de alecrim-do-campo foi o mais eficiente na redução do crescimento micelial de todos os fungos, com inibição completa quando se utilizou a concentração de 3000 mg L-1. A redução de crescimento variou de 29% (Fs) a 80% (Rs) a 250 mg L-1 do óleo essencial de alecrim-do-campo; a 500 mg L-1, variou de 29% (Fs) a 98% (Sr); e a 1000 mg L-1, de 41% (Fs) a 100% (Sr). A redução do crescimento dos fungos pelo óleo de aroeirinha na concentração de 3000 mg L-1 variou de 27% (Fsp) a 74% (Rs). Nessa concentração, o óleo de arnica-brasileira reduziu o crecimento micelial de Ss em 72%, o de Rs em 80% e o de Mp em 82%, sem efeitos significativos sobre o crescimento micelial de Fsp e Fop. Conclui-se que os óleos essenciais de alecrim-do-campo, aroeirinha e arnica-brasileira possuem potencial para o controle dos fungos fitopatogênicos estudados, com destaque para o óleo de alecrim-do-campo.

In addition to their value as therapeutic resources, medicinal plants also have the potential to be used as a source of alternative compounds against plant pathogens. The objective of this study was to evaluate the effect of essential oils extracted from the medicinal species Baccharis dracunculifolia, Schinus terebinthifolius and Porophyllum ruderale on the growth of the fungal plant pathogens Fusarium oxysporum f. sp. phaseoli (Fop), F. solani f. sp. phaseoli (Fsp), Sclerotinia sclerotiorum (Ss), S. minor (Sm), Rhizoctonia solani (Rs), Sclerotium rolfsii (Sr) and Macrophomina phaseolina (Mp). The radial mycelial growth of the fungi was evaluated on potato dextrose agar (PDA) in Petri dishes with five concentrations (0, 250, 500, 1000 and 3000 μL L-1) of the essential oils. Mycelial discs (5 mm diameter) of the growing colonies of each fungus were transferred to Petri dishes, which were maintained at 23 °C in the dark for 48 hours. The essential oil of B. dracunculifolia was the most effective oil in the reduction of the mycelial growth of all fungi. It completely inhibited their growth at 3000 mg L-1. At 250 mg L-1, the growth reduction caused by the oil of B. dracunculifolia varied from 29% (Fs) to 80% (Rs); at 500 mg L-1, it varied from 29% (Fs) to 98% (Sr); and at 1000 mg L-1, it varied from 41% (Fs) to 100% (Sr). The reduction of the mycelial growth caused by the oil of S. terebinthifolius at 3000 mg L-1 varied from 27% (Fsp) to 74% (Rs). At this concentration, the oil of P. ruderale reduced the mycelial growth of Ss by 72%, of Rs by 80% and of Mp by 82%, without significant effects on the mycelial growth of Fsp and Fop. We conclude that the essential oils of B. dracunculifolia, S. terebinthifolius and P. ruderale have the potential to be used to control the plant pathogens tested, especially the oil of B. dracunculifolia.

Adaptation and Resistance to Diseases in Brazil of Putative Sources of Common Bean Resistance to White Mold.

Common bean breeding programs for white mold (WM) resistance are in their initial stages in Brazil. Sources of partial resistance to WM are available abroad but their performance in Brazil is unknown. In two greenhouse (straw test) and three field experiments conducted in three districts in the state of Minas Gerais, Brazil, we evaluated a total of 23 lines with putative WM resistance with the objective to select lines with resistance to WM and other diseases associated with high yield potential. Two field-resistant local lines, two susceptible local cultivars, and two susceptible international lines were also included in the study. In the greenhouse, Cornell 605, A 195, and G122 were among the lines with the highest partial resistance to WM. In the field, these three lines were highly resistant to WM and had intermediate resistance or were resistant to anthracnose, angular leaf spot, rust, and Fusarium wilt. Cornell 605 and A 195 had high-yield potential but G122 yielded 47% less than the local lines under WM pressure. Our results suggest that Cornell 605 and A 195 are the most useful sources of resistance to WM for use in common bean breeding programs in Brazil.

Fungicide Sensitivity of Sclerotinia sclerotiorum: A Thorough Assessment Using Discriminatory Dose, EC50, High-Resolution Melting analysis, and Description of New Point Mutation Associated with Thiophanate-Methyl Resistance.

Thiophanate-methyl (TM), fluazinam, and procymidone are fungicides extensively used for white mold control of common bean in Brazil. We assessed the sensitivity of Brazilian isolates of Sclerotinia sclerotiorum to these three fungicides using discriminatory doses and concentration that results in 50% mycelial growth inhibition (EC50) values. In total, 282 isolates from the most important production areas were screened and none was resistant to fluazinam or procymidone. The EC50 values varied from 0.003 to 0.007 and from 0.11 to 0.72 µg/ml for fluazinam and procymidone, respectively. One isolate was resistant to TM. The EC50 of the TM-resistant isolate was greater than 100 µg/ml, whereas the EC50 of the sensitive isolates varied from 0.38 to 2.23 µg/ml. The TM-resistant isolate had a L240F mutation in the ß-tubulin gene. This is the first report of mutation at codon 240 causing resistance to a benzimidazole fungicide in S. sclerotiorum. The high-resolution melting analysis allowed the distinction of TM-sensitive and -resistant isolates by specific melting peaks and curves. The TM-resistant isolate had mycelial growth, sclerotia production, and aggressiveness comparable with that of the sensitive isolates, indicating that this genotype will likely compete well against sensitive isolates in the field. This study demonstrates that resistance to TM, fluazinam, and procymidone is nonexistent or rare. Resistance management practices should be implemented, however, to delay the spread of TM-resistant genotypes.

[Strategies in the treatment of supracondylar fractures of the humerus in children - proven and controversial]. / Behandlungsstrategien bei der suprakondylären Humerusfraktur im Kindesalter - Bewährtes und Kontroverses.

Elbow fractures are the 2nd most frequent fractures in children. Their therapy needs high expertise. Particularly an adequate analgesic therapy as well as an efficient and differentiated non-surgical or surgical therapy depending on the fracture type needs to be chosen. Secondary damage, especially growth disturbances, has to be prevented. Type I fractures can be managed conservatively with a cast. The crossed percutaneous pin fixation after open or closed reduction is the typical and most frequent surgical treatment option in supracondylar humeral fractures in children. Another good treatment option for supracondylar fractures type II to IV after closed reduction is the elastic-stable intramedullar nailing (ESIN). It is a minimally invasive treatment away from the fracture zone, which allows immediate free movement of the extremity. An immobilisation in a cast is therefore not necessary. That are the most possible effects (opinion of the authors) of the ESIN method, but discussed controversial in the literature. Especially neurovascular concomitant injuries require a differentiated treatment strategy to prevent long-term damage and should only be carried out in a specialised paediatric surgery unit. Long-term complications of supracondylar fractures are limitations in range of motion, nerval palsies, disturbances of growth, as well as cubitus varus (30 %) and valgus (3-7 %). These last ones often result from an insufficient initial anatomic reduction. The aim of the therapy should in any case be a patient-orientated treatment with the expected quickest recovery time and lowest long-term complications. Therefore supracondylar fractures should be treated only by a specialised paediatric trauma team, which can provide all non-surgical and surgical treatments. The spontaneous correcture is only seen in the sagittal view in young children between 6-7 years of age.

The kynurenine pathway: a missing piece in the puzzle of valproate action?

The present study was designed to determine the role of the kynurenine pathway (KP) in the mechanism of action of valproate (VPA). Therefore, we investigated changes in the concentrations of tryptophan (TRP), kynurenic acid (KYNA), and kynurenine (KYN) in the brain and plasma following VPA administration (50, 250 and 500mg/kg i.p.). The most important findings of our study were that VPA administration produced a progressive and strong increase in the central concentrations of KYNA, KYN and TRP. Simultaneously, the TRP level in plasma declined, while the peripheral increase of KYNA in plasma was weaker and occurred earlier than in the hippocampus. Bearing in mind that the observed effect may be a result of a strong VPA-induced displacement of TRP from its binding sites to plasma albumin, we checked the effect of ibuprofen (IBU) administration (a prototypic drug used to study drug binding to serum albumin) on the KP. We found that IBU evoked a similar pattern of change in the KP activity as VPA. These new findings indicate the existence of a mechanism that could stimulate the production of KYNA in the brain after VPA administration, and may partially contribute to the mechanisms of VPA action. The results of our experiment indicate that an increase in the brain's KYNA level may be achieved by TRP displacement from its binding site on plasma albumin with the administration of different drugs, including VPA, IBU, or short-chain fatty acids, with important clinical consequences.

Corticosterone modulates fear responses and the expression of glucocorticoid receptors in the brain of high-anxiety rats.

The aim of our experiments was to assess the effect of acutely administered corticosterone on the expression of glucocorticoid receptors (GRs) in the brain of rats with high (HR) and low (LR) levels of anxiety. The rats were divided into groups according to their conditioned fear-induced freezing responses and then were subjected to a second conditioned fear session one week after the initial fear conditioning. Immunocytochemical analysis revealed that the second exposure to contextual aversive stimuli resulted in higher levels of GRs expression in cingulate cortex area 1 (Cg1), the secondary motor cortex (M2) of the prefrontal cortex and the dentate gyrus of the hippocampus (DG) in LR rats compared with HR rats. The pretreatment of HR rats with corticosterone (20mg/kg, sc) increased the expression levels of GRs in Cg1, the M2 area and the DG to the levels observed in the LR vehicle group. The increase in the GRs levels was accompanied by a significant decrease in the conditioned fear response in the HR group. The control animals that were not exposed to aversive stimuli had similar levels of receptor-related immunoreactivity in all brain regions, and corticosterone did not change these expression levels. Our results suggest that HR animals may have deficits in the expression of stress-induced GRs in the prefrontal cortex and the DG. In addition, pretreatment with corticosterone increases the expression of GRs and normalizes the fear response in HR rats.

[Non-invasive estimation of intracranial pressure : MR-based evaluation in children with hydrocephalus]. / Nichtinvasive Bestimmung des intrakraniellen Drucks : MR-basierte Untersuchung bei Kindern mit Hydrozephalus.

CLINICAL/METHODICAL ISSUE: The intracranial pressure (ICP) is a crucially important parameter for diagnostic and therapeutic decision-making in patients with hydrocephalus. STANDARD RADIOLOGICAL METHODS: So far there is no standard method to non-invasively assess the ICP. Various approaches to obtain the ICP semi-invasively or non-invasively are discussed and the clinical application of a magnetic resonance imaging (MRI)-based method to estimate ICP (MR-ICP) is demonstrated in a group of pediatric patients with hydrocephalus. METHODICAL INNOVATIONS: Arterial inflow, venous drainage and craniospinal cerebrospinal fluid (CSF) flow were quantified using phase-contrast imaging to derive the MR-ICP. PERFORMANCE: A total of 15 patients with hydrocephalus (n=9 treated with shunt placement or ventriculostomy) underwent MRI on a 3 T scanner applying retrospectively-gated cine phase contrast sequences. Of the patients six had clinical symptoms indicating increased ICP (age 2.5-14.61 years, mean 7.4 years) and nine patients had no clinical signs of elevated ICP (age 2.1-15.9 years; mean 9.8 years; all treated with shunt or ventriculostomy). Median MR-ICP in symptomatic patients was 24.5 mmHg (25th percentile 20.4 mmHg; 75th percentile 44.6 mmHg). Median MR-ICP in patients without acute signs of increased ICP was 9.8 mmHg (25th percentile 8.6 mmHg; 75th percentile 11.4 mmHg). Group differences were significant (p < 0.001; Mann-Whitney U-test). ACHIEVEMENTS: The MR-ICP technique is a promising non-invasive tool for estimating ICP. PRACTICAL RECOMMENDATIONS: Further studies in larger patient cohorts are warranted to investigate its application in children with hydrocephalus.

Corticosterone attenuates conditioned fear responses and potentiates the expression of GABA-A receptor alpha-2 subunits in the brain structures of rats selected for high anxiety.

The aim of the experiment was to assess the effects of an acutely administered corticosterone on the expression of GABA-A receptor alpha-2 subunits in the brain structures of high (HR) and low (LR) anxiety rats (divided according to their conditioned fear-induced freezing response) subjected to a second conditioned fear session (1 week after fear conditioning). We found that corticosterone (20 mg/kg, sc) given to rats prior to the second conditioned fear session significantly enhanced a decrease in fear expression in the HR group. The behavioural effect of fear was accompanied by the increased expression of alpha-2 subunits in the basolateral amygdala (BLA) and the dentate gyrus of the hippocampus (DG) of the HR group. Corticosterone potentiated the effect of fear on alpha-2 subunit expression in the BLA, DG, the cingulate cortex area 1 and the secondary motor cortex (areas Cg1 and M2). The current study provides insight into the mechanisms that may be responsible for the beneficial effects of glucocorticoids in the therapy of some anxiety disorders.

Expression of N-methyl-D-aspartate (R)(GluN2B) - subunits in the brain structures of rats selected for low and high anxiety.

In this paper, we studied differences in the density of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits in the brains of low (LR) and high (HR) anxiety rats subjected to extinction trials and re-learning of a conditioned fear response, modeling a natural course of anxiety disorders. Classifications of animals as LR or HR was determined by fear-induced freezing responses in the contextual fear test. Increased basal concentrations of GluN2B subunits were observed in the amygdala of HR rats as compared to the unconditioned control group by Western blot analysis. Re-exposure of HR animals to the fear-conditioned context resulted in elevated concentrations of GluN2B subunits in the amygdala, hippocampus and the prefrontal cortex compared to LR rats as well as in the hippocampus and prefrontal cortex vs. the control group. In addition, it was shown that re-test of a conditioned fear increased the number of cells expressing GluN2B subunits in the basolateral amygdala, dentate gyrus of the hippocampus and secondary motor cortex (M2) in the HR group relative to the LR group. Together, these data suggest that animals that are more anxious have altered patterns of GluN2B subunit expression in the frontal cortex and limbic structures, which control emotional behaviour.

The effect of CRF2 receptor antagonists on rat conditioned fear responses and c-Fos and CRF expression in the brain limbic structures.

The influence of intracerebroventricular-administered selective corticotropin-releasing factor receptor 2 (CRF(2)) antagonists (antisauvagine-30, astressin-2B), on rat anxiety-like behavior, expression levels of c-Fos and CRF, and plasma corticosterone levels were examined in the present study. In fear-conditioned animals, both CRF receptor antagonists enhanced a conditioned freezing fear response and increased the conditioned fear-elevated concentration of serum corticosterone. Exogenously administered antisauvagine-30 increased the aversive context-induced expression of c-Fos in the 1 and 2 areas of the cingulate cortex (Cg1, Cg2), the central amygdala (CeA) and parvocellular neurons of the paraventricular hypothalamic nucleus (pPVN), and it enhanced the effect of conditioned fear in the secondary motor cortex (M2) and medial amygdala (MeA). Immunocytochemistry demonstrated an increase in CRF expression in the Cg1, M2 areas of the cortex, and pPVN, and it revealed the effect of conditioned fear in the CeA 35 min after antisauvagine-30 administration and 10 min after the conditioned fear test. Furthermore, astressin-2B, another CRF(2) receptor antagonist, enhanced expression of c-Fos and CRF in the CeA and pPVN, and revealed the effect of conditioned fear in the Cg1. These data support a model in which an excess in CRF(1) receptor activation, combined with reduced CRF(2) receptor signaling, may contribute to stronger expression of anxiety-like responses.

The localization of brain sites of anxiogenic-like effects of urocortin-2.

The influence of intracerebroventricullary-administered urocortin-2, a selective corticotropin-releasing factor receptor 2 (CRF(2)) agonist, on rat anxiety-like behaviour, the expression of c-Fos and CRF, and plasma corticosterone levels was examined in the present study. When applied to animals exposed to the conditioned fear-induced context, urocortin-2 enhanced a conditioned freezing fear response. Urocortin-2 also significantly decreased rat exploratory activity in the open field test. Exogenous urocortin-2 increased the conditioned fear-induced expression of c-Fos in the central amygdala (CeA), and parvocellular neurons of the paraventricular hypothalamic nucleus (pPVN), and revealed the effect of conditioned fear in the medial amygdala (MeA). In the fear-conditioned animals, immunocytochemistry showed an increase in the density of CRF-related immunoreactive complexes in the lateral septum (LS), 35min after urocortin-2 administration and 10min after the conditioned fear test, compared with saline-pretreated fear-conditioned animals. These data suggest a role of urocortin-2 in the behavioural and immunocytochemical responses to stress, in which it strengthens the measures of anxiety-like responses.

The opposite role of hippocampal mGluR1 in fear conditioning in kindled and non-kindled rats.

In the present paper, we analyzed the effects of hippocampal mGluR1 on the consolidation of a fear-conditioned response and on hippocampal glutamate and GABA concentration in rats subjected to the chemically-induced kindling of seizures. We hypothesized the important role of this glutamate receptor subpopulation in behavioural disturbances accompanying epilepsy. To this end, the behavioural and biochemical effects of selective mGluR1 and 5 receptor ligands were compared in sham and kindled animals (pentylenetetrazol-induced seizures). It was found that despite the fact that the freezing response to the aversively conditioned context was not changed by kindling itself, post-training intrahippocampal (dentate gyrus) injection of AIDA (a mGluR1 antagonist) oppositely influenced rat freezing behaviour in the non-kindled and kindled animals (i.e. the receptor ligand increased and decreased duration of the fear reaction, respectively). Kindling of seizures also enhanced the Glutamate/GABA ratio in the dorsal hippocampus (in vivo microdialysis), indicating an enhancement of excitatory processes in the brain. Altogether, the results showed that kindling of seizures led the potentiation of excitatory processes in the hippocampus, changing the role of the local mGluRs1 population in the conditioned fear learning.