Effect of Anesthesia in Stroke Models
Many investigators have examined or are examining the effects of focal and global cerebral ischemia on brain physiology, chemistry, and molecular aspects and function. Many animal and cellular models are utilized for these types of studies. However, anest
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1. Introduction Focal (stroke) and global (cardiac arrest) cerebral ischemia are major causes of death and disability and have been extensively investigated over the past 5 decades. Despite much animal work concerning brain tissue injury and identifying the multiple mechanisms by which focal and global cerebral ischemia produce neuronal injury, little of this work has been translated to effective treatment modalities in humans with ischemic injury. One possible reason for this may be that several important mechanisms of injury have been identified, and these mechanisms may be overlapping, making the issue of mechanisms extremely complex. Also, some mechanisms of injury may be critical in certain species but not in others, so certain heavily studied mechanisms of injury in rodents, for example, may be relatively unimportant in humans. Some mechanisms of injury from ischemia that have been heavily studied Ulrich Dirnagl (ed.), Rodent Models of Stroke, Neuromethods, vol. 47, DOI 10.1007/978-1-60761-750-1_10, © Springer Science+Business Media, LLC 2010
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are: production of oxygen free radicals, lipid peroxidation, release of excitatory amino acids (glutamate and aspartate), involvement of ionic pumps for Ca2+ and Na+ , acidosis, alterations in brain blood flow and metabolism, hyperthermia, involvement of genes and gene products, and others. The notion of protecting neurons from injury (neuroprotection) is not an innovative concept and is not new. Many purported neuroprotective agents such as anesthetics, free radical scavengers, excitatory amino acid antagonists, Ca2+ channel blockers, ionic pump modulators, anti-neutrophil and platelet factors, growth factors, hypothermia, and more recently, manipulation of genes and gene product and sex steroids have been investigated for years. Some of these have demonstrated varying degrees of success in certain species of animals, but none of these have been successful in humans, with the possible exception of hypothermia. The goal of this chapter is to discuss the most prominently used anesthetics in models of cerebral ischemia and their complicating role as neuroprotectants and/or neurotoxic agents. Finally, at the end of the chapter, we discuss the potential reasons why anesthetics and other pharmacologic agents have demonstrated little usefulness as neuroprotectants in humans following focal and global cerebral ischemia.
2. Anesthetic Neuroprotection Clinical observations that patients under general anesthesia were more tolerant of cerebral ischemia than unanesthetized patients (1) led to the idea that anesthetics may have an impact on brain injury following hypoxia or cerebral ischemia. Anesthetics have many mechanisms of action that have been associated with neuroprotection. These include: inhibition of spontaneous depolarization (2), cerebral blood flow redistribution (3, 4), antioxidant potential (5, 6), NMDA receptor antagonism (7, 8), and GABA potentiation (9–13). Anesthetic neuroprotection could be important, particularly in patients undergoing car
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