Permanent middle cerebral artery occlusion in sheep: a novel large animal model of focal cerebral ischemia.

As effective stroke treatment by thrombolysis is bound to a narrow time window excluding most patients, numerous experimental treatment strategies have been developed to gain new options for stroke treatment. However, all approaches using neuroprotective agents that have been successfully evaluated in rodents have subsequently failed in clinical trials. Existing large animal models are of significant scientific value, but sometimes limited by ethical drawbacks and mostly do not allow for long-term observation. In this study, we are introducing a simple, but reliable stroke model using permanent middle cerebral artery occlusion in sheep. This model allows for control of ischemic lesion size and subsequent neurofunctional impact, and it is monitored by behavioral phenotyping, magnetic resonance imaging, and positron emission tomography. Neuropathologic and (immuno)histologic investigations showed typical ischemic lesion patterns whereas commercially available antibodies against vascular, neuronal, astroglial, and microglial antigens were feasible for ovine brain specimens. Based on absent mortality in this study and uncomplicated species-appropriate housing, long-term studies can be realized with comparatively low expenditures. This model could be used as an alternative to existing large animal models, especially for longitudinal analyses of the safety and therapeutic impact of novel therapies in the field of translational stroke research.

Anatomical data on the craniocervical junction and their correlation with degenerative changes in 30 cadaveric specimens.

OBJECT: The goal of this project was to measure vertebral dimensions at the craniocervical junction and to investigate degenerative changes in this region and their correlations with the anatomical data. These studies will assist in an understanding of biomechanical conditions in this region, which are clinically relevant in cases of cervicogenic headaches and vertigo. METHODS: The authors examined 30 cadaveric specimens obtained from patients ranging in age from 24 to 88 years at death. Measurements of angles of the vertebrae were conducted using an imprint method. Microsections of osseous endplates and articular cartilage were graded according to their degrees of degeneration by using the Petersson classification (0, no sign of degeneration; I, superficial degeneration with several fragmentations; II, deeper degeneration with cartilaginous disintegration and penetrating ulceration; or III, complete cartilaginous degeneration with the appearance of subchondral bone in > 50% of the articular surface). The authors found Grade I changes in 100% of the occiput specimens. In the superior articular cartilage of C-1 no changes (Grade 0) were found in two specimens, whereas 6% of the specimens exhibited Grade II changes and 89% exhibited Grade I changes. In the inferior articular cartilage of C-1, 57% of the specimens displayed Grade I changes, 14% Grade II, and 20% Grade III changes. In the superior articular cartilage of C-2, 62.5% of the specimens displayed Grade I changes and 25% Grade II changes. At the occiput-C1 level the authors found a higher frequency of degeneration at the upper left articular surface of the atlas (Quadrants 1 and 3), and at the C1-2 level they found a higher frequency of degeneration at the upper left and upper right articular surfaces of the axis (Quadrants 2 and 3, respectively). Using the McNemar test, the authors investigated the frequency of affection of single quadrants in a left-right side comparison (lateral reversal). Significant differences were identified for Quadrant 2 of the upper left articular surface of C-2 and Quadrant 3 of the upper right articular surface of C-2. These results correlate with the analysis of single articular surfaces of the axis, but contradict the results for the atlas, in which no significant difference in the left-right side comparison was found. CONCLUSIONS: Severe degeneration in the atlantooccipital joints appears to be a rare condition, with no Grade II or III degeneration found in the occipital condyles and 6% Grade I, 89% Grade II, but no Grade III changes in the superior articular cartilage of the atlas. Degeneration of the inferior articular cartilage of C-1 and the superior articular cartilage of C-2 indicates that the atlantoaxial joint faces more intense mechanical exposure, which is increased at the upper joint surfaces.

[Cryotherapy of the brain--a new methodologic approach]. / Kryotherapie am Hirn--ein neuer methodischer Ansatz.

Cryodestruction of tissue is influenced by cooling and thawing rates, absolute tissue temperature, number of freeze-thaw cycles, and type of tissue. However, under clinical conditions a MRT visualization of the temperature distribution during cryo-procedures is not possible. Thus, the extent of necrotic areas within the cryo-influenced regions are not precisely predictable. This limitation is particularly relevant for the application of cryoablation in the brain. The present paper proposes the concept of a local, cryo-induced ischemic necrosis. The basic concept is that the MRT-observable and surgically well-manageable frozen region is ischemic. This cryo-induced ischemia causes a necrosis. The extent of the necrotic region is exclusively determined by the ischemia tolerance of the tissue. The effectiveness of this method is demonstrated on sheep brain in vivo. Compared to the freeze-thaw method, histological examinations show a sharper demarcation between regions of necrosis and healthy tissue. In conclusion, the method of MR-controlled local, cryo-induced ischemia enables an exact definition of the region of necrosis in the brain.