Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

Continued from Page 160reproduce the physical and biochemical behaviorof intact BBB, but most fail to reproduce thethree-dimensional nature of the in vivo barrierand do not allow concomitant exposure ofendothelial cells to abluminal (glia) and luminal(flow) influences. For this purpose, we havedeveloped a new dynamic in vitro blood-brainbarrier model (NDIV-BBB) designed to allow forextensive pharmacological, morphological andphysiological studies. This new dynamic modelof the BBB allows for longitudinal studies of theeffects of flow and co-culture in a controlledand fully recyclable environment that alsopermits visual inspection of the abluminalcompartment and manipulation of individualcapillaries. Further the system closely mimics thehemodynamic conditions present in pre- andpost-capillaries in vivo. Past and presentinvestigations include:• Development of new dynamic in vitro BBBmodels.• Molecular and cellular mechanisms ofblood-brain barrier induction and maintenance.• Molecular mechanism and site of action ofglucocorticoids.• Inflammatory processes at the BBB level,role of matrix metalloproteinase andproteinase inhibitors.• Isolation of human endothelial cells (EC)and human astrocytes.The Neurovascular Research LabThe Neurovascular Research Lab is heavilyinvolved in numerous research activities, such asbasic laboratory and applied animal research. Weoffer an outstanding environment for researchwith an infrastructure of research laboratoriesand animal facilities. Outstanding support isavailable for basic research and neurosiences withone of the best Cerebrovascular Centers in thecountry under the leadership of NeurologicalSurgery and Interventional Radiology departments.The laboratory specializes in research andanalysis of cerebral, abdominal and peripheralangiograms as well as MRI and CAT scan imagingon animals of all sizes. An excellent equipmentand variety of anesthetics allowing us to providea general anesthesia during a surgery/procedure aswell as monitoring and control of live functionsare available. The staff of the Laboratory andAnimal Husbandry Facility is LAC and GLPcertified. The Animal Critical Care Unit isavailable 24 hours a day, 7 days a week.Ongoing Current Projects:• Implantation of Encapsulated Islet Cells intoLiver/Gastric Wall (Diabetes).• Implantation of Encapsulated Tumor Cellsinto Brain.• Intrarterial Drug Delivery.• Blood Brain Barrier Damage in Stroke andIntracranial Hemorrhage.• Cerebral Aneurysms.• S-100 as a Serum Marker for distribution ofthe Blood Brain Barrier.• The Blood Brain Barrier and its Significancein Neuroimaging.• Markers of Blood Brain Barrier Formation.• Mechanisms of Osmotic Opening of theBlood Brain Barrier.Available Imaging Equipment:• MRI- SIEMENS (1.5 and 3T).• CT, CTA, CTP- SIEMENS 16.• Angiography- SIEMENS Angiostar (AxiomArtis BA and 3-D Reconstruction).157