A Word on Hypothermic Preconditioning

Abstract

We read the letter by Drs. T. A. Miyamoto and K. J. Miyamoto with interest, and we thank them for their interesting discussion of our study. They raised two issues for discussion. First, they wonder whether hypoxia/anoxia is a component of preconditioning stimuli to induce neuroprotective effects that were observed in our study.1Hypoxia/anoxia has been reported to produce preconditioning effects on the brain.2However, in our study, the brain slices were kept in a buffer that was gassed with 5% CO2–95% O2during the application of hypothermia. Control slices that were also kept in the oxygenated buffer but without having hypothermic preconditioning were used for comparison. In addition, it is generally accepted that hypothermia reduces cerebral metabolic rate and oxygen requirement. Therefore, we do not expect that brain slices during the application of hypothermia require more oxygen and have worse hypoxia (if it happens) than control slices. Therefore, we believe that the neuroprotective effects that we studied in our article are mainly attributed to hypothermic preconditioning. Of course, we cannot exclude the possibility that hypoxia plays a role in neuronal survival or death in our study. However, we hope that the proper controls performed in our study have isolated the hypothermic preconditioning–induced neuroprotection for us to study.Drs. T. A. Miyamoto and K. J. Miyamoto then suggest that intravenous application of taurine may be an alternative method for hypothermic preconditioning to provide neuronal protection against ischemia in clinical practice. This suggestion is interesting and may be practical. However, caution must be executed here because neuroprotection induced by hypothermic preconditioning and taurine are shown only in animal studies,1,3and it is not appropriate to extrapolate these data to humans. Although mild hypothermia that we used in our study is usually safe and easily achievable in clinical practice, more detailed animal studies are needed to show the effectiveness and safety of taurine application for brain ischemia before a clinical trial.4Nevertheless, we should keep our eyes open to any potential neuroprotective agents or methods such as hypothermic preconditioning or taurine application and vigorously test them for potential clinical use.Very few agents or methods have been shown to be effective and practical against brain ischemia in clinical studies in the field of neuroprotection. However, with studies aimed at the mechanisms of ischemic brain injury and neuroprotective methods, it is hoped that more molecular targets and, therefore, more agents with better selectivity to induce neuroprotection will be identified and tested for clinical use.* University of Virginia Health System, Charlottesville, Virginia. zz3c@virginia.edu