CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery.

The bed nucleus of the stria terminalis (BNST) is critical in mediating states of anxiety, and its dysfunction has been linked to stress-related mental disease. Although the anxiety-related role of distinct subregions of the anterior BNST was recently reported, little is known about the contribution of the posterior BNST (pBNST) to the behavioral and neuroendocrine responses to stress. Previously, we observed abnormal expression of corticotropin-releasing factor receptor type 2 (CRFR2) to be associated with post-traumatic stress disorder (PTSD)-like symptoms. Here, we found that CRFR2-expressing neurons within the pBNST send dense inhibitory projections to other stress-related brain regions (for example, the locus coeruleus, medial amygdala and paraventricular nucleus), implicating a prominent role of these neurons in orchestrating the neuroendocrine, autonomic and behavioral response to stressful situations. Local CRFR2 activation by urocortin 3 depolarized the cells, increased the neuronal input resistance and increased firing of action potentials, indicating an enhanced excitability. Furthermore, we showed that CRFR2-expressing neurons within the pBNST are critically involved in the modulation of the behavioral and neuroendocrine response to stress. Optogenetic activation of CRFR2 neurons in the pBNST decreased anxiety, attenuated the neuroendocrine stress response, ameliorated stress-induced anxiety and impaired the fear memory for the stressful event. Moreover, activation following trauma exposure reduced the susceptibility for PTSD-like symptoms. Optogenetic inhibition of pBNST CRFR2 neurons yielded opposite effects. These data indicate the relevance of pBNST activity for adaptive stress recovery.

Enriched environment impacts trimethylthiazoline-induced anxiety-related behavior and immediate early gene expression: critical role of Crhr1.

It has been shown previously (Sotnikov et al., ) that mice selectively inbred for high anxiety-related behavior (HAB) vs. low anxiety-related behavior in the elevated plus maze differentially respond to trimethylthiazoline (TMT), a synthetic fox fecal odor. However, less is known about whether environmental factors can rescue these extreme phenotypes. Here, we found that an enriched environment (EE) provided during early adolescence induced anxiolytic effects in HAB (HAB-EE) mice, rescuing their strong avoidance behavior induced by TMT. In a series of experiments, the contribution of maternal, juvenile and adolescent behavior to the anxiolytic effects elicited by EE was investigated. At the molecular level, using c-fos expression mapping, we found that the activity of the medial and basolateral amygdala was significantly reduced in HAB-EE mice after TMT exposure. We further analysed the expression of Crhr1, as its amount in the amygdala has been reported to be important for the regulation of anxiety-related behavior after EE. Indeed, in situ hybridisation indicated significantly decreased Crhr1 expression in the basolateral and central amygdala of HAB-EE mice. To further test the involvement of Crhr1 in TMT-induced avoidance, we exposed conditional glutamatergic-specific Crhr1-knockout mice to the odor. The behavioral response of Crhr1-knockout mice mimicked that of HAB-EE mice, and c-fos expression in the amygdala after TMT exposure was significantly lower compared with controls, thereby further supporting a critical involvement of Crhr1 in environmentally-induced anxiolysis. Altogether, our results indicate that EE can rescue strong avoidance of TMT by HAB mice with Crhr1 expression in the amygdala being critically involved.

[The significance of delayed diagnosis of lesions in multiply traumatised patients. A study of 1,187 shock room patients]. / Die Bedeutung von verzögert diagnostizierten Läsionen bei Polytraumatisierten. Eine Studie an 1187 Schockraumpatienten.

BACKGROUND: Multislice computed tomography (CT) technology has improved the diagnosis of relevant lesions within the phase of primary treatment of severely injured patients. The lack of time in this phase and the complexity of the multiple injuries there is still a risk that lesions will be missed at this stage. The purpose of this study was to evaluate the incidence, causes, implications and significance when injuries are not diagnosed until later. METHODS: The data were documented prospectively in the context of a quality management system for the care of severely injured patients in a primary urban trauma centre. Missed injuries were defined as any lesions that had not been recognised by the time the patient was admitted to the ICU. RESULTS: During a 44-month period 1,187 (ISS 21+/-17) patients were enrolled in the study, all of whom were admitted from May 1998 to April 2002 after attending the emergency room. In total 64 (4.9%) missed injuries were detected in 58 (ISS 30+/-16) patients; 26 of the 64 missed injuries were located on the torso, 8 injuries in the head and neck region, and 30 on the arms and legs. The missed injuries were categorised as follows: 1. Lesion not seen in diagnostics (n=15). 2. Incomplete diagnostics (n=8). 3. Primarily unsuspicuous examination (n=35). 4. Diagnostics interrupted due to hemodynamic instability (n=6). CONCLUSION: Despite intensified and standardised diagnostic procedures prescribed for use in trauma centres, injuries are still missed in severely injured patients. About 30% of lesions that are not diagnosed until after the patient has left the emergency room have clinically significant, but not lethal, consequences for the patient. Great importance attaches to the follow-up investigation on the intensive care station, so that lesions that have initially been overlooked can be diagnosed and treated as soon as possible so as to keep the complication rate low.

Biliodigestive anastomosis after intraoperative irradiation in swine.

A large animal model was established to investigate the feasibility and suitable dosage of intraoperative radiation therapy (IORT) to the hepatic hilum before biliary-enteric anastomosis is performed. Twenty-two Pietrain Hampshire pigs underwent gallbladder and proximal bile duct resection followed by IORT using 20-40 Gy and performing biliary-enteric anastomosis. In the follow-up period of 56 days, pigs developed dose-dependent complications like stenosis of the biliary-enteric anastomosis. Results demonstrate that IORT of the liver hilum up to 20 Gy is safe with acceptable early complications in the presented animal model. The porcine biliary-enteric anastomosis can tolerate intraoperative irradiation up to a dosage of 40 Gy without disruption.