Abstract Background Septic encephalopathy is frequent but its pathophysiology is enigmatic. We studied expression of neurotransmitters, inflammation and integrity of the blood–brain barrier (BBB) in several brain regions during abdominal sepsis. We compared mice with either lethal or surviving phenotype in the first 4 sepsis days. Mature CD-1 females underwent cecal ligation and puncture (CLP). Body temperature (BT) was measured daily and predicted-to-die (within 24 h) mice (for P-DIE; BT < 28 °C) were sacrificed together (1:1 ratio) with mice predicted-to-survive (P-SUR; BT > 35 °C), and healthy controls (CON). Brains were dissected into neocortex, cerebellum, midbrain, medulla, striatum, hypothalamus and hippocampus. Results CLP mice showed an up to threefold rise of serotonin in the hippocampus, 5-hydroxyindoleacetic and homovanillic acid (HVA) in nearly all regions vs. CON. Compared to P-SUR, P-DIE mice showed a 1.7 to twofold rise of HVA (386 ng/g of tissue), dopamine (265 ng/g) and 3,4-Dihydroxyphenylacetic acid (DOPAC; 140 ng/g) in the hippocampus, hypothalamus and medulla (174, 156, 82 ng/g of tissue, respectively). CLP increased expression of TNFα, IL-1β and IL-6 mRNA by several folds in the midbrain, cerebellum and hippocampus versus CON. The same cytokines were further elevated in P-DIE vs P-SUR in the midbrain and cerebellum. Activation of astrocytes and microglia was robust across regions but remained typically phenotype independent. There was a similar influx of sodium fluorescein across the BBB in both P-DIE and P-SUR mice. Conclusions Compared to survivors, the lethal phenotype induced a stronger deregulation of amine metabolism and cytokine expression in selected brain regions, but the BBB permeability remained similar regardless of the predicted outcome.

Surgical sealants help achieve rapid haemostasis when applied as an adjunct to sutures in vascular surgery, but their use can lead to various side effects. This study compared the local inflammatory reaction to commercially available BioGlue and Coseal sealants in a rabbit aorta suture hole model. Twenty male New Zealand white rabbits were randomised to testing with either BioGlue or Coseal. Two weeks after sealant application to suture holes, sections of the aorta at the puncture site, and surrounding tissue, were processed for histopathological analysis. Inflammation was graded from 0 to 3 according to tissue alteration and presence of inflammatory cells. Material stiffness was measured in vitro using compression testing. From examination of the inflammatory response to the sealants, a less severe histopathological assessment score was assigned to the Coseal compared to the BioGlue group (mean +/- SD: 1.56 +/- 0.53 vs 2.67 +/- 0.50; p = 0.002). While both materials triggered a typical foreign body reaction characterised by granulomatous inflammation, BioGlue additionally provoked eosinophilic cell infiltration. Lymphocytes, plasma cells and B cells were also more prevalent in the BioGlue compared to the Coseal specimens. Coseal residue was either absent or visible in only small quantities, while significant BioGlue deposits remained in the tissue 2 weeks after application. Coseal was much more elastic than BioGlue, with a compressive modulus an order of magnitude lower (mean +/- SD: 91 +/- 41 vs 1833 +/- 297 kPa). Compared to BioGlue, Coseal elicited a less pronounced inflammatory response in the aortic and peri-aortic tissue in this model, and demonstrated greater elasticity.

Nitric oxide is implicated in modulation of memory and pharmacological as well as genetic inhibition of neuronal nitric oxide synthase (nNOS) leads to impaired cognitive function. We therefore decided to study learning and memory functions and cognitive flexibility in the Morris water maze (MWM) in 1-month-old male mice lacking nNOS (nNOS KO). Hippocampal protein profiling was carried out to possibly link protein derangement to impaired cognitive function. Two-dimensional gel electrophoresis with in-gel digestion of spots and subsequent MALDI-TOF identification of proteins and quantification of proteins using specific software was applied. In the memory as well as in the relearning task of the MWM, most of the nNOS KO failed to find the submerged platform within a given time. Proteomic evaluation of hippocampus, the main anatomical structure computing cognitive functions, revealed aberrant expression of a synaptosomal associated protein of the exocytotic machinery (NSF), glycolytic enzymes, chaperones 78 kDa glucose-regulated protein, T-complex protein 1; the signaling structure guanine nucleotide-binding protein G(I)/G(S)/G(T) and heterogeneous nuclear ribonucleoprotein H of the splicing machinery. We conclude that nNOS knockout mice show impaired spatial performance in the MWM, a finding that may be either linked to direct effects of nNOS/NO and/or to specific hippocampal protein derangements.