Experimental Models of Discovery: Prediction and Protection must Proceed “Hand-in-Hand”

Kenneth      Maiese

doi:10.2174/156720207780637225

Abstract

With the continued expansion of medical technologies and new strategies for human disease, we can sometimes fall prey to the belief that successful clinical therapies will consistently employ the desired attributes of safety and efficacy as common denominators. Yet, even for some remarkable and presumably safe diagnostic techniques such as magnetic resonance imaging, these assumptions may fall short of our actual experience. For example, there exist potential adverse effects of exposure to elevated magnetic field levels that exist during magnetic resonance imaging. It is true that magnetic fields occur naturally throughout the planet, but human derived magnetic fields can further enhance the intensity of naturally occurring magnetic fields. Industries that involve railways operating from direct current electrical supply sources or that employ magnetic levitation train systems can lead to the exposure of significant magnetic fields. In addition, commercial activities related to aluminum or steel production using intensified alternating currents also can result in magnetic fields that may be beyond normal human tolerance. In the healthcare system, magnetic resonance imaging for diagnostics can easily generate increased magnetic fields that may pose risks for both magnetic resonance imaging technicians and the patients under evaluation. Adverse affects from strong magnetic fields are multifaceted and can result in the acute onset of gastric distress, nausea, and vertigo. In regards to more long-term effects, magnetic field exposure has been tied to cerebral neoplasms, lung carcinoma, and hematological cancers. Some studies have suggested that exposure to magnetic fields can increase the risk of spontaneous abortions. More recent work involving magnetic resonance imaging previously published in this journal adds further concern to potential developmental abnormalities with magnetic field exposure by demonstrating in rodents exposed to a 1.5 T magnetic resonance image field for one week the subsequent onset of reference memory deficits (Yang et al., 2007). It should be noted that further work especially with more rigorous controls and statistically powered clinical trials is required, since some prior investigations did not exclude for the effects of confounding variables such as concurrent toxic substance exposure. So how does one develop new therapies that will offer efficacy for disease treatment, but also will not harm the afflicted individual patient? Early scientific investigation has provided us with both a clear vision and a solid foundation for future discovery. During the 1700s, Antoine Lavoisier, Karl Scheele, and Joseph Priestley independently relied upon a variety of experimental models to illustrate that air and its component oxygen were vital to sustain processes associated with combustion as well as life. Lavoisier subsequently carried this work further with animal models to illustrate that oxygen based upon concentration and duration of exposure could be either beneficial or toxic to an organism. These early models of experimentation laid some of the groundwork for todays science and the critical reliance upon both cell and animal models for the investigation of the etiology and treatment of human disease processes. Present models of human disease have become so diverse in nature that it would be almost inconceivable for one to foresee from several years past that the genetic construction of cell lines or the reliance upon aquatic animal models could for the most part accurately predict and sharply focus therapeutic strategies for a wide range of clinical disorders. This issue of Current Neurovascular Research serves to highlight the vantage points of a broad discipline of experimental models that promote the development of basic research to the realities of clinical care. In original and review articles, unique strategies describe the use of fused embryonic rodent neurons with neuroblastoma cell lines, the deployment of embryonic, neuronal, and adult mesenchymal stem cells for chronic neurodegenerative disorders, the development of ischemic animal models for furthering the understanding of the cellular pathways that occur during stroke and Alzheimers disease, and the burgeoning reliance upon the Zebrafish model for a host of human disorders. Although it is unlikely that any single experimental model of human disease will ever be capable of replicating the complex disease processes of the human body, it is clear that the visionary minds of Lavoisier, Scheele, and Priestley have led us upon an exciting path of discovery coupled with great insight and we are enthusiastic in this issue of Current Neurovascular Research to hopefully foster this same course for our readers today.

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