| Popis: |
Background and aims: In stroke, the effectiveness of experimental cell therapy has recently been demonstrated in rodent models. There is optimism that cell therapy has the potential to overcome a current dilemma (apart from thrombolysis in acute stage) in stroke therapy: so far most alternative therapeutic strategies including about 60 neuro-protective drugs which had likewise proven efficacious in pre-clinical rodent studies, subsequently failed in clinical trials. This demonstrates that translation of new stroke therapies into clinical application requires close-to-practice models, i.e. large animal models of focal cerebral ischemia. Existing primate models are cost intensive, restricted to highly specialized breeding facilities and limited by ethical considerations. Therefore, we developed a new, cost-effective stroke model in sheep that allows to create variable, but reproducible lesion sizes / neurological dysfunctions. Methods: 25 adult Merino rams were randomly a ssigned to one of five groups: transcranial 1-branch- (n=5), 2-branch- (n=5) or total middle cerebral artery occlusion (MCAO, n=5), sham operation (n=5) and control group (no operation, n=5). Following exposure of the left MCA, the vessel was occluded or touched (sham) by high frequency bipolar forceps. Animals underwent an analgesic and antibiotic treatment for 7 days. Neurological investigation was performed before surgery and at days 1, 4, 7, 10, 16, 25, 32 and 42 following MCAO according to a house-designed score point system. Further, effects of MCAO were evaluated by magnetic resonance imaging (MRI) including T1-, T2-, T2*-sequences, diffusion weighted (DW) imaging and magnetic resonance angiography (MRA) using a Philips 1,5T clinical scanner at days 1, 14 and 42. In addition, positron emission tomography (PET) was performed at days 14 and 42. Animals were killed at day 43 post operation and brains were removed for neuropathological investigation. Results: Total MCAO results in a large cortica |
