Neuroimmune crosstalk in the central nervous system and its significance for neurological diseases

The central nervous system (CNS) is now known to actively communicate with the immune system to control immune responses both centrally and peripherally. Within the CNS, while studies on glial cells, especially microglia, have highlighted the importance of this cell type in innate immune responses of the CNS, the immune regulatory functions of other cell types, especially neurons, are largely unknown. How neuroimmune cross-talk is homeostatically maintained in neurodevelopment and adult plasticity is even more elusive. Inspiringly, accumulating evidence suggests that neurons may also actively participate in immune responses by controlling glial cells and infiltrated T cells. The potential clinical application of this knowledge warrants a deeper understanding of the mutual interactions between neurons and other types of cells during neurological and immunological processes within the CNS, which will help advance diagnosis, prevention, and intervention of various neurological diseases. The aim of this review is to address the immune function of both glial cells and neurons, and the roles they play in regulating inflammatory processes and maintaining homeostasis of the CNS.Peer reviewe

Intestinal Epithelial Sirtuin 1 Regulates Intestinal Inflammation During Aging in Mice by Altering the Intestinal Microbiota

Intestinal epithelial homeostasis is maintained by complex interactions among epithelial cells, commensal gut microorganisms, and immune cells. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD), but the mechanisms of this process are not clear. We investigated how Sirtuin 1 (SIRT1), a conserved mammalian NAD+-dependent protein deacetylase, senses environmental stress to alter intestinal integrity. Methods We performed studies of mice with disruption of Sirt1 specifically in the intestinal epithelium (SIRT1 iKO, villin-Cre+, Sirt1flox/floxmice) and control mice (villin-Cre-, Sirt1[superscript flox/flox]) on a C57BL/6 background. Acute colitis was induced in some mice by addition of 2.5% dextran sodium sulfate to drinking water for 5–9 consecutive days. Some mice were given antibiotics via their drinking water for 4 weeks to deplete their microbiota. Some mice were fed with a cholestyramine-containing diet for 7 days to sequester their bile acids. Feces were collected and proportions of microbiota were analyzed by 16S rRNA amplicon sequencing and quantitative PCR. Intestines were collected from mice and gene expression profiles were compared by microarray and quantitative PCR analyses. We compared levels of specific mRNAs between colon tissues from age-matched patients with ulcerative colitis (n=10) vs without IBD (n=8, controls). Results Mice with intestinal deletion of SIRT1 (SIRT1 iKO) had abnormal activation of Paneth cells starting at the age of 5–8 months, with increased activation of NF-κB, stress pathways, and spontaneous inflammation at 22–24 months of age, compared with control mice. SIRT1 iKO mice also had altered fecal microbiota starting at 4–6 months of age compared with control mice, in part because of altered bile acid metabolism. Moreover, SIRT1 iKO mice with defective gut microbiota developed more severe colitis than control mice. Intestinal tissues from patients with ulcerative colitis expressed significantly lower levels of SIRT1 mRNA than controls. Intestinal tissues from SIRT1 iKO mice given antibiotics, however, did not have signs of inflammation at 22–24 months of age, and did not develop more severe colitis than control mice at 4–6 months. Conclusions In analyses of intestinal tissues, colitis induction, and gut microbiota in mice with intestinal epithelial disruption of SIRT1, we found this protein to prevent intestinal inflammation by regulating the gut microbiota. SIRT1 might therefore be an important mediator of host–microbiome interactions. Agents designed to activate SIRT1 might be developed as treatments for IBDs. Keywords: IBD; mouse model; microbiome; bacteri

Temporal Trends in the Use of Computed Tomographic Pulmonary Angiography for Suspected Pulmonary Embolism in the Emergency Department : A Retrospective Analysis.

Recently, validated clinical decision rules have been developed that avoid unnecessary use of computed tomographic pulmonary angiography (CTPA) in patients with suspected pulmonary embolism (PE) in the emergency department (ED). To measure any resulting change in CTPA use for suspected PE. Retrospective analysis. 26 European EDs in 6 countries. Patients with CTPA performed for suspected PE in the ED during the first 7 days of each odd month between January 2015 and December 2019. The primary end points were the CTPAs done for suspected PE in the ED and the number of PEs diagnosed in the ED each year adjusted to an annual census of 100 000 ED visits. Temporal trends were estimated using generalized linear mixed regression models. 8970 CTPAs were included (median age, 63 years; 56% female). Statistically significant temporal trends for more frequent use of CTPA (836 per 100 000 ED visits in 2015 vs. 1112 in 2019; P < 0.001), more diagnosed PEs (138 per 100 000 in 2015 vs. 164 in 2019; P = 0.028), a higher proportion of low-risk PEs (annual percent change [APC], 13.8% [95% CI, 2.6% to 30.1%]) with more ambulatory management (APC, 19.3% [CI, 4.1% to 45.1%]), and a lower proportion of intensive care unit admissions (APC, -8.9% [CI, -17.1% to -0.3%]) were observed. Data were limited to 7 days every 2 months. Despite the recent validation of clinical decision rules to limit the use of CTPA, an increase in the CTPA rate along with more diagnosed PEs and especially low-risk PEs were instead observed. None specific for this study