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Background & Aims Neuroinflammation in the gut is associated with many gastrointestinal (GI) diseases, including inflammatory bowel disease. In the brain, neuroinflammatory conditions are associated with blood-brain barrier (BBB) disruption and subsequent neuronal injury. We sought to determine whether the enteric nervous system is similarly protected by a physical barrier and whether that barrier is disrupted in colitis. Methods Confocal and electron microscopy were used to characterize myenteric plexus structure, and FITC-dextran assays were used to assess for presence of a barrier. Colitis was induced with dextran sulfate sodium, with co-administration of liposome-encapsulated clodronate to deplete macrophages. Results We identified a blood-myenteric barrier (BMB) consisting of extracellular matrix proteins (agrin and collagen-4) and glial end-feet, reminiscent of the BBB, surrounded by a collagen-rich periganglionic space. The BMB is impermeable to the passive movement of 4 kDa FITC-dextran particles. A population of macrophages is present within enteric ganglia (intraganglionic macrophages [IGMs]) and exhibits a distinct morphology from muscularis macrophages, with extensive cytoplasmic vacuolization and mitochondrial swelling but without signs of apoptosis. IGMs can penetrate the BMB in physiological conditions and establish direct contact with neurons and glia. Dextran sulfate sodium-induced colitis leads to BMB disruption, loss of its barrier integrity, and increased numbers of IGMs in a macrophage-dependent process. Conclusions In intestinal inflammation, macrophage-mediated degradation of the BMB disrupts its physiological barrier function, eliminates the separation of the intra- and extra-ganglionic compartments, and allows inflammatory stimuli to access the myenteric plexus. This suggests a potential mechanism for the onset of neuroinflammation in colitis and other GI pathologies with acquired enteric neuronal dysfunction.

We provide evidence for the compartmentalization of the avian thymic medulla and identify the avian thymic dendritic cell. The thymic anlage develops from an epithelial cord of the branchial endoderm. Branches of the cord are separated by primary septae of neural crest origin. The dilation of the primary septae produces the keratin-negative area (KNA) of the thymic medulla and fills the gaps of the keratin-positive network (KPN). Morphometric analysis indicates that the KNA takes up about half of the volume of the thymic medulla, which has reticular connective tissue, like peripheral lymphoid organs. The KNA receives blood vessels and in addition to pericytes, the myoid cells of striated muscle structure occupy this area. The myoid cells are of branchial arch or prechordal plate origin providing indirect evidence for the neural crest origin of the KNA. The marginal epithelial cells of the KPN co-express keratin and vimentin intermediate filaments, which indicate their functional peculiarity. The basal lamina of the primary septum is discontinuous on the surface of the KPN providing histological evidence for the loss of the blood-thymus barrier in the medulla. In the center of the KNA, the dendritic cells lie in close association with blood vessels, whereas the B-cells accumulate along the KPN. The organization of the KPN and KNA increases the "surface" of the so-called cortico-medullary border, thereby contributing to the efficacy of central tolerance.

In the medulla of bursal follicle, only the secretory dendritic cell ( BSDC ) is furnished with secretory machinery. The granular discharge of BSDC appears in membrane-bound and solubilized forms. Movat pentachrome staining proves that the solubilized form is a glycoprotein, which fills up the extracellular space of follicular medulla. The glycoprotein contributes to bursal microenvironment and may be attached to the surface of medullary lymphocytes. The secretory granules of BSDC may be fused, resulting in large, irregular dense bodies, which are the first sign of BSDC transformation to macrophage-like cells ( Mal ). To determine the effect of infectious bursal disease virus ( IBDV ) infection on the extracellular glycoprotein and BSDC, SPF chickens were experimentally infected with IBDV. On the surface of BSDC, the secretory substance is in high concentration, which may contribute to primary binding of IBDV to BSDC. The early distribution of IBDV infected cells is in consent with that BSDC. The IBDV infected BSDC rapidly transforms to Mal in which the glycoprotein staining appears. In the dense bodies, the packed virus particles inhibit the virus particles preventing the granular discharge, which may represent the first, early phase of virus replication cycle. The absence of extracellular glycoprotein results in alteration in the medullary microenvironment and subsequently B cell apoptosis. On the surface of medullary B cells, the solubilized secretory substance can be in much lower concentration, which results in secondary binding of IBDV to B cells. In secondary, late phase of virus replication cycle, the virus particles are not packed in electron dense substance which results in cytolytic lymphocytes and presence of virus in extracellular space. The Mal emigrates into the cortex, where induces inflammation, recruiting heterophil granulocyte and monocyte.

Leukocyte scintigraphy (LS) was performed in 20 pediatric patients with inflammatory bowel disease (IBD: 10 with ulcerative colitis, 2 with indeterminate colitis, and 8 with Crohn disease) in different stages of clinical activity. Leukocytes were separated from 15 to 60 ml venous blood and were labeled in vitro with [99mTc]HM-PAO. The segmental extent (small intestine; ascending, transverse, and descending colon; and recto-sigmoideum) of the process was determined by LS. The uptake of each bowel segment was scored in relation to the bone marrow uptake. The scintigraphic activity, calculated by summing the segment scores, was compared with laboratory parameters. The mean labeling efficacy was 76% (60-86%). The segmental extent of the process determined by LS was compared with the results of barium enema or colonoscopy with regard to 32 bowel segments. The sensitivity, specificity, and accuracy of LS were 93, 88, and 91%, respectively. Two extraintestinal manifestations (abdominal abscess and joint involvement) were also detected by LS. These lesions were verified by computed tomography (CT) (abscess) and on the basis of the clinical outcome (arthritis). The scintigraphic activity correlated with the C-reactive protein (CRP) level (r = 0.82, p < 0.001), the alpha 2-globulin level (r = 0.63, p < 0.02), the sedimentation rate (r = 0.51, p < 0.05), and the fS iron level (r = -0.66, p < 0.005). LS is applicable in pediatric patients. The method is an excellent technique for assessment of the extent of IBD in children. Extraintestinal manifestations of IBD can also be investigated by LS. The scintigraphic activity is a useful parameter for determination of the activity of IBD in children.