No abstract

The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutaneously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.

Summary: The present study was undertaken to corre late calcium accumulation with the development of neu ronal necrosis following transient ischemia. After ) 0 min of forebrain ischemia in the rat-a period that leads to reproducible damage of CAl pyramidal celis-determi nation of calcium concentration and evaluation of mor phological signs of cell body necrosis in the dorsal hippo campus were performed at various recirculation times. Tissue calcium concentration was not different from con trol at the end of ischemic period and did not change after 3, 6, 12, or 24 h of recirculation. However, after 48 h, calcium content increased significantly, with a further inBased on data showing accumulation of calcium in irreversibly damaged tissue and on results dem onstrating massive sequestration of calcium by mitochondria, the hypothesis of calcium-related cell death was advanced for cardiac tissue (Fleck enstein, 1977;Borgers, 1981), skeletal muscle (Wrogemann and Pena, 1976; Leonard and Sal peter, 1979), and liver (Schanne et ai. , 1979). In these hypotheses, it was tacitly assumed that one major mechanism of cell death was mitochondrial calcium overload, with ensuing structural damage and secondary energy failure. However, it was rec ognized that the adverse effects of calcium encom passed activation of neutral proteases (Guroff, 1964) and of phospholipases (Sun and Su, 1979).In recent years, it has been realized that the loss of calcium hemostasis may be an important mecha nism of ischemic brain damage (Haas, 1981;Siesj6, 1981) cumulation of polyenoic free fatty acids (FFAs) and their oxidative conversion products, and by trig gering proteolysis, protein phosphorylation, and disaggregation of cytoskeletal components (for ref erences see Siesj6 and Wieloch, 1985). One inter esting feature of the hypothesis of calcium-related damage as applied to the brain relates to the fact that neurons differ in the density of calcium channels, with some pyramidal cells having a dense population of agonist-operated channels in their dendritic fields. As at least some of these cells could be identical to those reported to be selec tively vulnerable to several different insults (see Siesj6, 1981;Wieloch, 1985), one has the interesting possibility that the calcium overload could help to explain not only neuronal necrosis in general, but also selective neuronal vulnerability.It has been demonstrated that ischemic insults that lead to irreversible damage are accompanied by net accumulation of calcium in the tissue (Yana gihara and McCall, 1982; Hossmann et aI. , 1983;Dienel, 1984). However, published results give no indication of whether calcium accumulates before cell necrosis occurs or occurs as a secondary phe nomenon to an irreversible injury. One previous study, in which 45Ca autoradiography and tissue 90 1. K. DESHPANDE ET AL.sampling were employed, gives information on re sidual calcium accumulation following 30 min of forebrain ischemia in the rat (Dienel, 1984). As his topathological evolution of cell damage as a result of th...

Hospitals vary in organisational culture, and the type of culture relates to the safety climate within the hospital. In combination with prior studies, these results suggest that a healthcare organisation's culture is a critical factor in the development of its patient safety climate and in the successful implementation of quality improvement initiatives.