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Cerebrovascular diseases such as stroke, intracerebral hemorrhages or vascular dementia are a significant and common cause for morbidity and mortality in our today’s industrial nations. In addition to clinical studies in the experimental field we focus particularly on the comprehension of pathophysiological processes after cerebral ischemia and the promotion of regeneration and rehabilitation of the affected tissue. All cells are embedded in a matrix which consists of specific molecules. These cells are integrated in the interaction among neurons, endothelial cells, astrocytes and microglia of the brain diversely.
When areas of the brain have been damaged neuronal progenitor cells are activated which develop into differentiated neuronal cells. These have a neuroprotective and growth stimulating impact on the damaged brain areas. Thus the idea is obvious to replace the destroyed cells - for instance in a stroke model – by administering stem cells. As a model of chronic vascular damages and a vascular neurodegenerative disease we have established a cerebral amyloid mouse model (CAA-model) in our laboratory which does not only develop ß-amyloid in the brain parenchyma (like other Alzheimer’s models), but also shows a relevant amyloid deposition in the vessels.
Current studies indicate that it results in a stronger blending of pathophysiological processes in the neurodegeneration than previously assumed and that there is a cross-talk among amyloid, vessel damages and neurodegeneration.
- What role is played by matrix metalloproteinases in the damage and regeneration in stroke
- How do iron oxide particle-marked stem cells interact in the injured brain after vessel injection and can their mobility, horning and disposition in the brain be observed using the 9.4T MRI in-vivo?
- Can effects on an ß-amyloid vessel interaction be proved in longitudinal studies in the CAA model and when can they be influenced therapeutically?
- Can by employing the transcranial ultrasound resp. the HIFU-method (High-intensity-focused-ultrasound) effects on the blood-brain-barrier, transport processes or even regeneration processes be observed or influenced by using high field MRI technology?
- Reuter B, Rodemer C, Grudzenski S, Meairs S, Bugert P, Hennerici MG, Fatar M. Effect of simvastatin on mmps and timps in human brain endothelial cells and experimental stroke. Transl Stroke Res. 6:156-159; 2015.
- Reuter B, Grudzenski S, Chatzikonstantinou E, Meairs S, Ebert A, Heiler P, Schad LR, Staufenbiel M, Hennerici MG, Fatar M. Thrombolysis in experimental cerebral amyloid angiopathy and the risk of secondary intracerebral hemorrhage. Stroke. 45:2411-2416; 2014.
- Baier S, Krämer P, Grudzenski S, Fatar M, Kirsch S, Schad LR. Chlorine and sodium chemical shift imaging during acute stroke in a rat model at 9.4 tesla. MAGMA. 27:71-79;2014.
- Ansar S, Chatzikonstantinou E, Wistuba-Schier A, Mirau-Weber S, Fatar M, Hennerici MG, Meairs S. Characterization of a new model of thromboembolic stroke in c57 black/6j mice. Transl Stroke Res. 5:526-533; 2014.
- Reuter B, Rodemer C, Grudzenski S, Couraud PO, Weksler B, Romero IA, Meairs S, Bugert P, Hennerici MG, Fatar M. Temporal profile of matrix metalloproteinases and their inhibitors in a human endothelial cell culture model of cerebral ischemia. Cerebrovasc Dis. 35:514-520;2013.
- Alonso A, Reinz E, Leuchs B, Kleinschmidt J, Fatar M, Geers B, Lentacker I, Hennerici MG, de Smedt SC, Meairs S. Focal delivery of aav2/1-transgenes into the rat brain by localized ultrasound-induced bbb opening. Mol Ther Nucleic Acids. 2:e73; 2013.
- Schwarzbach CJ, Schaefer A, Ebert A, Held V, Bolognese M, Kablau M, Hennerici MG, Fatar M. Stroke and cancer: The importance of cancer-associated hypercoagulation as a possible stroke etiology. Stroke. 43:3029-3034; 2012.
- Kreisel SH, Stroick M, Reuter B, Senn E, Hennerici MG, Fatar M. Mmp-2 concentrations in stroke according to etiology: Adjusting for enzyme degradation in stored deep-frozen serum and other methodological pitfalls. J Clin Neurosci. 19:1564-1567; 2012.
- Fatar M, Stroick M, Griebe M, Marwedel I, Kern S, Bieback K, Giesel FL, Zechmann C, Kreisel S, Vollmar F, Alonso A, Back W, Meairs S, Hennerici MG. Lipoaspirate-derived adult mesenchymal stem cells improve functional outcome during intracerebral hemorrhage by proliferation of endogenous progenitor cells stem cells in intracerebral hemorrhages. Neurosci Lett. 443:174-178; 2008.
- Giesel FL, Stroick M, Griebe M, Tröster H, von der Lieth CW, Requardt M, Rius M, Essig M, Kauczor HU, Hennerici MG, Fatar M. Gadofluorine m uptake in stem cells as a new magnetic resonance imaging tracking method: An in vitro and in vivo study. Invest Radiol. 41:868-873; 2006.
Prof. Dr. Marc Fatar
Neurology University Hospital
Medical Faculty Mannheim
Phone +49 621 383-3953