ALTERED GENE-EXPRESSION IN CEREBRAL-ISCHEMIA

Background: Using the techniques of molecular biology, recent experimental studies have shown that cerebral ischemia induces a variety of changes in gene expression in the brain. Summary of Review: During the early postischemic stages, protein synthesis in the brain is generally suppressed, but specific genes are expressed and their corresponding proteins may be synthesized, such as immediate-early gene products (c-fos, c-jun, and zinc finger gene), heat-shock proteins, and amyloid precursor protein. The ability of neurons to induce such stress responses, which depends on both the severity of ischemia and the intrinsic nature of the neuronal populations, may be directly associated with neuronal death and survival after ischemia. Nerve growth factor and fibroblast growth factor are also induced after ischemia and may be related to repair processes, in which a role of glial cells is suggested. Postischemic events that may be associated with the altered gene expression include (1) induction of tolerance to ischemia after pretreatment with sublethal ischemia, (2) slow, progressive neuronal changes and the development of neuronal plasticity after ischemia, and (3) delayed neuronal changes in remote areas outside the cerebral ischemic focus. Conclusions: Because a variety of harmful stresses, including ischemia, elicit the same stress response and because this response is induced when total protein synthesis in the brain is nearly completely suppressed, this response may be vital to cell survival and repair. A successful induction of this response may induce resistance and survival of neurons after ischemia. However, failure or abortion of the response and persistent stresses may lead to neuronal death and possibly long-term changes and degeneration.