Morphological Assessments of Global Cerebral Ischemia: Electron Microscopy

Ischemic stroke in humans often results in acute and delayed neuronal death, as well as a wide range of chronic neurological deficits. In order to understand neuronal loss and neurological deficits after brain ischemia, several animal models have been established, including global and focal ischemic models. Transient cerebral ischemia leads to neuronal death that does not occur immediately, but takes place after 2–3 days of vascular reperfusion, the so-called delayed neuronal death. During this 2–3 days’ delay period, all neurons destined to die appear normal under the light microscope. At the ultrastructural level, however, dramatic dissociation of polyribosomes, protein aggregation, and organelle damage takes place in postischemic neurons undergoing delayed neuronal death. Delayed neuronal death also occurs in the penumbral area after focal ischemia. The delay period provides a window of opportunity for understanding the underlying pathological processes and for developing therapies. This chapter describes the methods of transmission electron microscopy in the context of morphological studies of brain ischemia.