Exploratory investigation of intestinal function and bacterial translocation after focal cerebral ischemia in the mouse

The gut communicates with the brain bidirectionally via neural, humoral and immune pathways. All these pathways are affected by acute brain lesions, such as stroke. Brain-gut communication may therefore impact on the overall outcome after CNS-injury. Until now, contradictory reports on intestinal function and translocation of gut bacteria after experimental stroke have been published. Accordingly, we aimed to specifically investigate the effects of transient focal cerebral ischemia on intestinal permeability, gut associated lymphoid tissue and bacterial translocation in an exploratory study using a well-characterized murine stroke model. Methods: After 60 min of middle cerebral artery occlusion (MCAO) we assessed intestinal morphology (time points after surgery day 0, 3, 5, 14, 21) and tight junction protein expression (occludin and claudin-1 at day 1 and 3) in 12-week-old male C57BI/6J mice. Lactulose/mannitol/sucralose test was performed to assess intestinal permeability 24-72 h after surgery. To investigate the influence of cerebral ischemia on the local immune system of the gut, main immune cell populations in Peyer's patches (PP) were quantified by flow cytometry. Finally, we evaluated bacterial translocation to extraintestinal organs 24 and 72 h after MCAO by microbiological culture and fluorescence in situ hybridization targeting bacterial 16S rRNA. Results: Transient MCAO decreased claudin-1 expression in the ileum but not in the colon. Intestinal morphology (assessed by light microscopy) and permeability did not change measurably after MCAO. After MCAO, animals had significantly fewer B cells in PP compared to naive mice. Conclusions: In a murine model of stroke, which leads to large brain infarctions in the middle cerebral artery territory, we did not find evidence for overt alterations neither in gut morphology, barrier proteins and permeability nor presence of intestinal bacterial translocation

Validation study of HSCL-10, HSCL-6, WHO-5 and 3-key questions in 14–16 year ethnic minority adolescents

Background There is a lack of validated instruments for detection of depression in ethnic minority adolescent patients in primary care. This study aimed to compare a subgroup of the bilingual, ethnic minority adolescents with the rest of the population using Hscl-10, Hscl-6, WHO-5 and 3-Key Questions for detection of depression in primary care. Method This is a cross-sectional, multicenter study conducted in General Practice in Norway and Denmark. A minor bilingual non-aggregated heterogenic ethnic minority group from non-European countries was compared with a major ethnic group of Norwegian/Danish adolescents. Participants completed questionnaires which were either mailed to them or found on our website. The Composite International Diagnostic Interview was used as gold standard. Depression classified by the International Classification of Diseases - 10. The Internal and external validity of the four questionnaires were examined. Optimal cut-off point for major depressive disorder was calculated using the Youden Index. Results 294 (77 %) were interviewed; mean age was 15 years. The ethnic group comprised 44 (64 % girls and 36 % boys). Chronbach’s alpha was above 0. 70 and area under curve was 0.80 or above for all instruments in the ethnic minority group. Cut-off points for major depressive disorder had sensitivities of 81 % (Hscl-10), 82 % (Hscl-6), 91 % (Who-5) and 81 % (3-key questions) in the ethnic minority group. Corresponding specificities were 80 % (Hscl-10), 77 % (Hscl-6), 80 % (Who-5) and 67 % (3-key questions). Cut-off points were the same Hscl-10, Who-5, the 3-key questions but differed for Hscl-6. Conclusion Hscl-10, Hscl-6, WHO-5 and 3-key questions seem to be valid instruments for detection of depression in bilingual, ethnic minority adolescents in primary care