Neuronal tolerance to O2 deprivation in drosophila: novel approaches using genetic models

In spite of many advances in monitoring oxygenation and preventing cerebro-vascular accidents, there is still considerable morbidity and mortality from conditions with cerebral blood flow impairment and O2 deprivation leading to hypoxic/ischemic brain injury. Part of this failure is related to the complexity of the cascade of events that ensue after hypoxia or ischemia, but also part of it may be related to the fact that most research in the previous few decades has focused, justifiably, on cerebral vessel disease. However, an important aspect of the cascade is dependent on many factors that are inherent to the nature and response of the tissue itself. Hence, there is more need now for a two-pronged approach to hypoxic/ischemic brain injury, one focusing on vessel disease, its prevention, and treatment, and the other centering on the brain tissue itself and the factors that render neurons and glia more susceptible or more tolerant to a lack of oxygenation. In the past several years, a number of methods, techniques, and animal models have been used to address the response of neurons and glia to lack of oxygen. In this review, we highlight some novel ideas and some results that we and others have obtained, mostly pertaining to the genetic endowment and responses of the central nervous system to O2 deprivation. The role and importance of genetic models, such as the Drosophila melanogaster, are discussed, and an example illustrating how to harness the power of Drosophila genetics is detailed.