Many animal studies of cerebral ischemia are conducted under anesthetic conditions. Two major problems arise in considering the use of anesthesia, and these problems may confound the results obtained. The first concerns the fact that investigators use different anesthetics and analgesics for different species; second, considerable literature supports the idea that anesthetics themselves are neuroprotectant. The theory that anesthesia may have an impact on brain injury following hypoxia or cerebral ischemia is derived from clinical observations that patients under general anesthesia were more tolerant of ischemia than unanesthetized patients (40 ). Ischemia may be affected by anesthetics via multiple potential mechanisms, including neuroprotection. The mechanisms by which anesthetics produce anesthesia and the pharmacologic characteristics of anesthetics make them likely neuroprotective candidates; these include involvement of NMDA receptors (41), involvement of gamma amino-butyric acid (GABA) A and B receptors (42,43), reduction of oxidative stress (44), inhibition of spontaneous depolarizations in the ischemic penumbra (45), and favorable redistribution of cerebral blood flow (46). Anesthetics have also been demonstrated to increase tolerance of brain to a subsequent ischemic insult (ischemic tolerance) (47) . Many investigations of the effects of anesthetics on brain are problematic, because most of these reports have compared various anesthetics to each other, making interpretation of the effect of any one anesthetic difficult or impossible (16). Anesthetics have rarely been compared or evaluated with the unanesthetized state, and only a few studies have evaluated the neuroprotective properties of anesthetics when administered following ischemia onset or at reperfusion. A major problem in those investigations of the effects of neuroprotectants with anesthetized animals is that anesthetics themselves have their own effect on the cerebral vasculature, brain metabolism, brain electrophysiology, temperature, and blood pressure. Generally, patients with stroke or cardiac arrest are not anesthetized at the time of the ischemic event. Thus, whether ischemia in preclinical anesthetized species will mimic ischemic events that occur in awake humans is unlikely.

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