Bioenergetics of cerebral ischemia: A cellular perspective
Section snippets
Introduction: brain ischemia injures all brain cells
Twenty-five years ago it was shown that brain ischemia only produces edema in cerebral cortex when damage of astrocytes and endothelial cells has occurred, i.e., an infarct has been formed (or is forming), whereas neuronal necrosis alone was insufficient for edema formation (Petito et al., 1982, Plum, 1983). This was a time when the roles of non-neuronal cells in normal and abnormal function had begun to attract interest, including their reactions to ischemia (Hertz, 1981). It is now realized
Cellular composition of brain
Both neurons and non-neuronal cells are made up of subgroups, e.g., neurons releasing and/or expressing receptors for different transmitters, the glial cells astrocytes, oligodendrocytes, microglia, and NG2 cells (previously regarded as oligodendrocyte precursors, but now recognized as a separate cell type, also called synantocytes; Butt et al., 2005); and capillary endothelial cells). Each cell type displays a variety of subcellular structures, in most cells including processes that are
Focal ischemia
Interruption of the supply of oxygen and glucose following blockade of an artery leads to focal ischemia. Unless rapid recanalization occurs, an infarction comprising all cell types begins to develop in the center of the lesion and is fully developed within 1–3 days (Du et al., 1996). Surrounding the infarcted core is a penumbra, which suffers less severe reduction of blood flow because of collateral circulation, and cells here may survive, contingent upon recirculation within a few hours.
Mature brain
Most patients suffering a middle cerebral artery occlusion also have white matter damage (Ho et al., 2005). Consistent with a lower metabolic rate in white matter than in gray matter, both the normal rate of cerebral blood flow and the infarction threshold for cerebral blood flow are lower than in gray matter (Marcoux et al., 1982, Bristow et al., 2005, Demchuk and Mitchell, 2005, Arakawa et al., 2006). However, during permanent artery occlusion in the rat, morphologic changes in subcortical
Concluding remarks
In spite of the different mechanisms by which brain cells die, most or all all succumb to bioenergetic failure, brought about by an increased intracellular Na+ concentration, shown to cause metabolic exhaustion in several cell types, and exacerbating the effects of energy-deprivation per se (Table 5). In most cases the increased Na+ concentration is combined with dysregulation of cytosolic Ca2+ concentration, following NMDA receptor-gated Ca2+ entry and/or reverse operation of the Na+/Ca2+
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