Cerebral Ischemia: From Animal Studies to Clinical Practice. Should the Methods Be Reviewed?

Abstract

The development of experimental models of focal cerebral ischemia has allowed for a better knowledge of its pathophysiology and for testing therapeutic strategies. However, most neuroprotective substances giving favorable results in these models have later not been shown to be clinically effective. This could be explained by several reasons. First, the homogeneity obtained in animal models in order to achieve results is not seen in clinical practice in humans, in whom a given pathological condition may show a high variability depending on several parameters. This makes it difficult to achieve groups of patients sufficiently large and homogeneous to obtain valid conclusions in the clinical trials. The lack of agreement between the experimental studies and the clinical practice can also be explained by other reasons, such as the methods of the experimental model itself; by the fact that the methods to assess results in these models are not comparable to those used in clinical practice; by pathophysiological differences between experimental animals and man, and even by the fact that the substances tested have different pharmacological properties in the different species. These disadvantages must not invalidate preclinical neuroprotection studies. Rather, the knowledge of the reasons for divergences with the clinical situation can help to optimize experimental models so that both become actually comparable, and the laboratory results can be confirmed by clinical studies.