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Inadequate preclinical testing (e.g., rodent studies) has been partly blamed for the failure of many cytoprotectants to effectively treat stroke in humans. For example, some drugs went to clinical trial without rigorous functional and histological assessment over long survival times. In this study, we characterized recent experimental practices in rodent cytoprotection experiments to determine whether the limitations of early studies have been rectified.
We identified 138 rodent cytoprotection studies published in several leading journals (Journal of Neuroscience, Stroke, Journal of Cerebral Blood Flow and Metabolism and Experimental Neurology) for 2000 - 2002 and compared these to those published in 1990. From each study we determined the ischemia model, age and sex of the animal, the histological and functional endpoints used, and the methodology used to assess intra- and postischemic temperature.
Ninety-eight percent of recent studies used young adult rodents and most used males. Most studies (60%) did not assess functional outcome and survival times were often ≤ 48 hr (66%) for focal ischemia and ≤ 7 days (80%) for global ischemia. Over 60% of the experiments relied solely upon rectal temperature during ischemia and only 32.6% of ischemia studies measured temperature after surgery. The 1990 data were similar.
Many investigators ignore the need to assess long-term functional and histological outcome and do not accurately represent clinical conditions of ischemia (e.g., use of aged animals). In addition, intra- and postischemic temperature measurement and control is frequently neglected or inadequately performed. Further clinical failures are likely.
Computerized tomography scans are rapid, readily available, and relatively inexpensive. Volume of hemorrhage on computerized tomography (CT) is an important predictor of mortality and functional ability after intracerebral hemorrhage (ICH). Computerized tomography angiography (CTA) offers many clinical advantages over cerebral digital subtraction angiography (DSA) for the evaluation of intracranial vascular abnormalities in cases of ICH. CTA must be shown to have similar sensitivity and specificity as DSA in the detection of secondary causes of ICH. The use of non-contrast CT in the initial evaluation of patients presenting with suspected ICH is well established and universally accepted. Recently, advances in CTA have enabled this modality to gain wide acceptance in evaluating possible secondary causes of ICH, such as aneurysm or vascular malformation. As scanner technology and software rendering capabilities continue to improve, CTA appears poised to replace DSA and become the new gold standard for such evaluations.