Drug Doses

Considering the different models of cerebral ischemia and different species used for ischemia studies, it is essential to determine the appropriate concentration of neuroprotective drug to use. Oftentimes, the test drug is administered only at a single dose level, not at high, medium, and low doses, which permits dose-response evaluation of drug-specific putative effects. Dose-response curves for neuroprotection are extremely important to generate but are often neglected in preclini-cal studies. To be fair, however, one reason that dose-response curves are often not incorporated into preclinical studies is the usually minimal financing available from the pharmaceutical industry for these types of studies. Dose-response development was illustrated by work performed on the 21-aminosteroid agent tirilazad (36). This drug has a vitamin E-like scavenging effect on lipid peroxide radicals, it is a potent scavenger of oxygen radicals (superoxide anion), and it stabilizes membranes. Dose-response characteristics of tirilazad were evaluated in a global ischemia dog model (36). Cerebral perfusion pressure was controlled to a level of ischemia of approximately

Table 1 Global and Focal Models of Cerebral Ischemia

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