Morphology of tissue damage caused by permanent occlusion of middle cerebral artery in mice

In two series of experimental occlusion of the middle cerebral artery (MCA) in mice, the time course and the evolution of morphological changes were followed. Both series comprised control animals used in experiments for the screening of neuroprotective and therapeutic effects after focal ischemia. In both series the left MCA was permanently occluded and the animals were sacrificed by perfusion fixation at certain time intervals following occlusion. In the first series the follow up was continued until the 30th day after ischemia. In the second, the observation period was extended to two months. The general question was addressed, whether or not such experimental settings can contribute to the understanding of cellular (necrosis vs apoptosis) and tissue (resorption vs scar) reaction. In the two series the technical procedures were only slightly different. Nevertheless, the development of morphological sequelae was at variance. Differences in tissue reaction in both sets revealed features that were rarely observed in previous protocols. In the first series, infarct areas were different in size, often a central part near the meninges was preserved and gave rise to a prominent mesenchymal reaction. In the second series, infarcts had almost constant size and mesenchymal reaction changes were minimal. The end product in both series, however, was a shallow groove much smaller than the primary well-demarcated defect. We conclude that minor technical variations of MCA occlusion in the mouse demonstrate the variability of occlusion sequelae due to collateral irrigation known from human cerebral pathology. On the cellular level, neuronal death is obviously completed during the first 24 hours in the infarct core. Thus, the mechanism of neuronal damage can only be best observed by morphology at the transition between completed territorial necrosis and unchanged tissue: shrunken neuronal perikarya develop into pycnotic nuclei, that may be interpreted as apoptosis. A second area of partial damage is marked by gliosis. Astrocytic reaction extended far beyond the infarct border, even to the contralateral hemisphere and could represent a component of size compensation.