Geofrey De Visscher

At present, resting state functional MRI (rsfMRI) is increasingly used in human neuropathological research. The present study aims at implementing rsfMRI in mice, a species that holds the widest variety of neurological disease models. Moreover, by acquiring rsfMRI data with a comparable protocol for anesthesia, scanning and analysis, in both rats and mice we were able to compare findings obtained in both species. The outcome of rsfMRI is different for rats and mice and depends strongly on the applied number of components in the Independent Component Analysis (ICA). The most important difference was the appearance of unilateral cortical components for the mouse resting state data compared to bilateral rat cortical networks. Furthermore, a higher number of components was needed for the ICA analysis to separate different cortical regions in mice as compared to rats.

Development of multimodal imaging strategies is currently of utmost importance for the validation of preclinical stem cell therapy studies.

Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications. Searching for mechanisms potentially useful to overcome these complications, we have established the signaling role of monocytes/macrophages in the development of FBR and the presence of CD34⁺ cells that potentially differentiate into myofibroblasts. Therefore, CD68⁺ cells were in vitro activated with fibrinogen and also purified from the FBR after 3 days of implantation in rats. Gene expression profiles showed a switch from monocytes and macrophages attracted by fibrinogen to activated macrophages and eventually wound-healing macrophages. The immature FBR also contained a subpopulation of CD34⁺ cells, which could be differentiated into myofibroblasts. This study showed that macrophages are the clear driving force of FBR, dependent on milieu, and myofibroblast deposition and differentiation.

Large animal research, often required as a final phase before commencing clinical trials for devices, has generally been hampered by the lack of appropriate tools to compare it with either initial small animal tests or to later evaluation in humans. Setting out to tissue engineer heart valves, we were particularly struck by the limited availability of immunohistochemical markers for sheep tissue, despite sheep being the FDA-approved animal for heart valve testing. This paper, therefore, aims to compile the available knowledge and extend the marker list with antibodies cross-reacting with sheep tissue. Thirty-seven antibodies attributed to 1 of these classes were found to be useful: (1) endothelium, (2) mesenchymal cells, myofibroblasts, and smooth muscle cells, (3) immune response, (4) primitive cells, (5) extracellular matrix, and (6) miscellaneous. Twelve had already been used in sheep tissue, but to our knowledge, the remaining 25 have not been described for use in sheep. From this result, we can conclude that the immunohistochemical panel for sheep has been extensively expanded with respect to cardiovascular research.

Intracranial pressure (ICP) monitoring is indispensable in the assessment of neurotrauma in humans and animal models. It was shown that cerebellar ICP, leaving the cortical area intact, can replace cerebral ICP in rats. While cerebral probes may induce spreading depression, the effects of a miniature erebellar probe on near infrared spectroscopy (NIRS) measurements and cerebral hemodynamics are not known. We therefore compared a group with an ICP probe to a control group. Our experiments revealed decreased optical path lengths at 840 nm and 960 nm (both p=0.026) and a decreased cerebral blood flow (CBF, p=0.015). Despite these changes, the data found using NIRS agree with the blood sample analysis. An increased deoxyhemoglobin concentration (p=0.041) and a decreased sagittal sinus oxygen saturation (p=0.041), were found in the ICP probe group. Because the decreased CBF was accompanied by an increased arterio-venous oxygen difference (p=0.026) and unaltered cerebral metabolic rate of oxygen (p=0.485), this suggests an uncoupling. These data suggest that a cerebellar miniature Codman® ICP probe induces an uncoupling of cerebral metabolism and CBF. In addition, NIRS is found to be a robust technique: even when path lengths are altered after probe insertion, physiological alterations can still be examined.