ABSTRACT
Stroke and cardiac arrest represent the third leading cause of death and disability in the United States. These diseases strike some 1,400,000 Americans annually, and a high mortality is associated with both. For stroke and cardiac arrest, probably 30% and 50% of individuals, respectively, die immediately, with a large percentage of survivors suffering from severe disability. In fact, stroke itself is the leading cause of disability in the United States and costs the most in terms of health care. Most strokes and cardiac arrests occur in older patients (over 65 years of age); however, a marked increase has been observed in stroke incidence in patients between 45 and 65 years of age ( 1 ). Thus, the high incidence and signifi cant morbidity and mortality associated with these diseases and the brain dysfunction in these critically ill patients emphasize the need to identify and test neuroprotective strategies that will be effective in protecting the brain from hemodynamic stressors, such as hypotension and shock states, and in minimizing ischemic damage from stroke and cardiac arrest. The aims of neuroprotection are to optimally match cerebral blood fl ow with metabolic demand and to stop the complicated pathophysiologic cascades of cellular and molecular events that lead to neuronal, glial, and vascular cell death. Despite ample animal research over the past fi ve decades concerning the pathophysiology of brain injury from ischemia, very little of this work has translated into effective treatment modalities for stroke or cardiac arrest in humans ( 2 ). Clinical trials designed to test a variety of neuroprotective agents that have had excellent outcomes in preclinical experimental animal studies have been disappointing. This chapter will discuss some of the potential reasons for the diffi culty and lack of success involved in attempting to translate positive experimental results with neuroprotective agents from animals to humans.
