Functional recovery after experimental spinal cord compression and whole body vibration therapy requires a balanced revascularization of the injured site.

PURPOSE: Based on several positive effects of whole-body-vibration (WBV) therapy on recovery after SCI, we looked for correlations between functional (analysis of locomotion), electrophysiological (H-reflex) and morphological (density of functioning capillaries) measurements after SCI and WBV-treatment. METHODS: Severe compression SCI at low-thoracic level (T8) in adult female Wistar rats was followed by WBV twice a day (2 × WBV) over a 12-week post-injury period. Intact rats and rats with SCI but no WBV-therapy ("No-WBV") served as controls. Recovery of locomotion was determined by BBB-locomotor rating, foot stepping angle (FSA), rump-height index (RHI), correct ladder steps (CLS) and H-reflex at 1, 3, 6, 9, and 12 weeks after SCI. Animals were sacrificed by an overdose of Isoflurane (Abbott). One hour later their spinal cords were fixed in 4% PFA for 24 h. Samples from the thoracic cord containing the lesion site and from the lumbar intumescence were cut into 10 µm thick longitudinal frozen sections. RESULTS: All functioning capillaries were unequivocally identified because the endogenous peroxidase of the erythrocytes was clearly visualized with 0.05% diaminobenzidine (DAB). A determination of their absolute (in µm2) and proportional areas (percent of photographed tissue) revealed a significantly denser capillary network in the WBV-treated rats: 1,66 ± 0,41% in the "vibrated" rats versus 0,79 ± 0,19% in the "No-WBV" animals. The portion of the capillary network in intact rats was 1,51 ± 0,69%. Surprisingly, even though the vascularization in the treated animals was significantly increased, this had no beneficial influence on the recovery of functions after SCI. CONCLUSION: The results of this study provide for the first time evidence that intensive WBV-therapy leads to a significantly denser capillary network in the lesioned spinal cord. However, since this higher capillary density is not associated with improved functional recovery (possibly because it exceeded the balance necessary for functional improvements), optional treatments with lower intensity or less time of WBV-therapy should be tested.

In vivo MRI stem cell tracking requires balancing of detection limit and cell viability.

Cell-based therapy using adult mesenchymal stem cells (MSCs) has already been the subject of clinical trials, but for further development and optimization the distribution and integration of the engrafted cells into host tissues have to be monitored. Today, for this purpose magnetic resonance imaging (MRI) is the most suitable technique, and micron-sized iron oxide particles (MPIOs) used for labeling are favorable due to their low detection limit. However, constitutional data concerning labeling efficiency, cell viability, and function are lacking. We demonstrate that cell viability and migratory potential of bone marrow mesenchymal stromal cells (BMSCs) are negatively correlated with incorporated MPIOs, presumably due to interference with the actin cytoskeleton. Nevertheless, labeling of BMSCs with low amounts of MPIOs results in maintained cellular function and sufficient contrast for in vivo observation of single cells by MRI in a rat glioma model. Conclusively, though careful titration is indicated, MPIOs are a promising tool for in vivo cell tracking and evaluation of cell-based therapies.

Diverticular disease is associated with an enteric neuropathy as revealed by morphometric analysis.

BACKGROUND: The pathogenesis of diverticular disease (DD) is attributed to several aetiological factors (e.g. age, diet, connective tissue disorders) but also includes distinct intestinal motor abnormalities. Although the enteric nervous system (ENS) is the key-regulator of intestinal motility, data on neuropathological alterations are limited. The study aimed to investigate the ENS by a systematic morphometric analysis. METHODS: Full-thickness sigmoid specimens obtained from patients with symptomatic DD (n = 27) and controls (n = 27) were processed for conventional histology and immunohistochemistry using anti-HuC/D as pan-neuronal marker. Enteric ganglia, nerve and glial cells were quantified separately in the myenteric, external and internal submucosal plexus compartments. KEY RESULTS: Compared to controls, patients with DD showed significantly (P < 0.05) (i) reduced neuronal density in all enteric nerve plexus, (ii) decrease of ganglionic nerve cell content in the myenteric plexus, (iii) decreased ganglionic density in the internal submucosal plexus, (iv) reduced glial cell density in the myenteric plexus, (v) decrease of ganglionic glial cell content in the myenteric plexus and increase in submucosal plexus compartments, (vi) increased glia index in all enteric nerve plexus. About 44.4% of patients with DD exhibited myenteric ganglia displaying enteric gliosis. CONCLUSIONS & INFERENCES: Patients with DD show substantial structural alterations of the ENS mainly characterized by myenteric and submucosal oligo-neuronal hypoganglionosis which may account for intestinal motor abnormalities reported in DD. The morphometric data give evidence that DD is associated with structural alterations of the ENS which may complement established pathogenetic concepts.

Activation of cortical and inhibited differentiation of medullary epithelial cells in the thymus of lymphotoxin-beta receptor-deficient mice: an ultrastructural study.

The reciprocal influences of thymic lymphocyte and nonlymphocyte populations, i.e. thymic cross-talk, are necessary for the proper maturation of thymocytes and the development/maintenance of thymic stromal microenvironments. Although the molecular influences exerted by thymic stromal cells on maturing thymocytes have been extensively studied, the identity of signalling molecules used by thymocytes to influence the thymic stromal cells is still largely unknown. Our study provides the first ultrastructural evidence that the functional lymphotoxin-beta receptor (LTbetaR) signalling pathway is engaged in the cross-talk between thymocytes and the thymic stromal cell population. We show that LTbetaR signalling is of the utmost significance for the preservation of the subcellular integrity of all thymic epithelial cells. In the absence of LTbetaR there is (1) hypertrophy and activation of cortical thymic epithelial cells, (2) the complete loss of fully differentiated medullary thymic epithelial cells, and (3) the inhibited differentiation of remaining medullary thymic epithelial cells with the appearance of prominent intercellular cysts in the thymic medulla.