The development of experimental models of focal cerebral ischemia has allow
ed for a better knowledge of its pathophysiology and for testing therapeuti
c strategies. However, most neuroprotective substances giving favorable res
ults 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 pract
ice in humans, in whom a given pathological condition may show a high varia
bility depending on several parameters. This makes it difficult to achieve
groups of patients sufficiently large and homogeneous to obtain valid concl
usions in the clinical trials. The lack of agreement between the experiment
al 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 th
e methods to assess results in these models are not comparable to those use
d in clinical practice; by pathophysiological differences between experimen
tal animals and man, and even by the fact that the substances tested have d
ifferent pharmacological properties in the different species, These disadva
ntages must not invalidate preclinical neuroprotection studies. Rather, the
knowledge of the reasons for divergences with the clinical situation can h
elp to optimize experimental models so that both become actually comparable
, and the laboratory results can be confirmed by clinical studies. Copyrigh
t (C)2001 S. Karger AG, Basel.