From the Editor's Perspective: Activity, Anoxia, Angiogenesis, and Alzheimer's Disease

For a body of work to eventually be designated as a “Landmark” article may require years of analysis, further investigative support, and frequent citations in future articles. In this issue of Current Neurovascular Research, we are introducing the publication of pioneering original articles in combination with “state-of the-art” review articles that may someday be considered significant building blocks for future lines of investigation. In several respects, the articles focus upon the ability of ischemic cell injury to not only lead to acute or chronic nervous system impairment in a variety of disorders, but also to actively generate reparative processes that may even result from activities considered as simple as physical exercise. Our original articles in this issue offer a unique perspective upon the central nervous system's ability to respond to hypoxicischemic injury. The initial article by He et al. demonstrates that even during periods of severe ischemia to regions of the brain that are exquisitely sensitive to injury, such as the hippocampus, progenitor stem cells are actively generated that may lead to a viable repair process. Furthermore, the severity of injury may be predicted by the analysis of postural changes that can be associated with the degree of stem cell induction. Work from Ding et al. in our second original article illustrates that in animals subjected to physical exercise prior to a focal ischemic insult, both cerebral infarct volume and neurological disability are significantly reduced. These observations support the premise that pre-ischemic exercise can reduce cellular injury. Further cellular analysis by this group of authors also suggests that the beneficial effects of exercise may be secondary to the induction of new vessel formation through angiogenesis. Our review articles in this issue form a perfect complement to the original manuscripts and begin with an article from Ronen Leker and Ron McKay that discusses the use and therapeutic potential of endogenous neural stem cells for disease entities such as stroke, Alzheimer's disease, and Parkinson's disease. Nakamichi et al. take us next into the cellular world of ischemic injury and consider the potential relationship between central nervous system ferrous ion metabolism and the modulation of the Nmethyl- D-aspartate receptor. The role of cerebral ischemic injury is further examined by Ryszard Pluta with an alternative hypothesis that proposes that repetitive ischemic-reperfusion insults may form the basis for development of chronic neurodegenerative disorders, such as Alzheimer's disease. This process may occur by increasing the sensitivity of neurons to amyloid formation, aberrant amyloid precursor protein processing, and presenilin expression. Lephart et al. follow suit in their article by revealing the unusual role that dietary phytoestrogens, primary components in a variety of soy foods, may play during vascular, neuroendocrine, and cognitive dysfunction. Given that phytoestrogens act as selective estrogen receptor modulators, these authors suggest that dietary phytoestrogens will have a substantial role in the etiology, pathophysiology, and treatment of cardiovascular and neurodegenerative diseases. Our final article in this issue by Sergio Rey and Rodrigo Iturriaga moves us from the cellular mechanisms that may determine vascular integrity to the level of the carotid body as the principal arterial chemoreceptor. They provide us with evidence that endothelins and free radicals, such as nitric oxide, can modulate carotid body chemoreception by modulating vascular tone, cerebral blood flow, and oxygen delivery to chemoreceptor cells to potentially influence a variety of nervous system functions. With the introduction of pioneering original articles to complement our cutting edge review manuscripts that together focus upon the components of activity, anoxia, angiogenesis, and Alzheimer's disease, we are proud to present this issue as our “Landmark” and hope that in the future the very articles that comprise this issue will themselves be considered “Landmark” pieces of work in their own right.