[Neuroprotection in stroke. A critical overview]

Cerebral ischemia leads to a cascade of pathophysiological processes which contribute to ischemic cell damage. In addition to the excitotoxicity, which is characterized by a massively elevated extracellular concentration of excitatory amino acids and an intracellular overload with calcium, the increased formation of free radicals, the inflammation and the apoptosis are also involved in ischemic damage. Neuroprotection, a pharmacological interaction with these pathophysiological processes, is one possibility to attenuate the consequences of cerebral ischemia. In experimental studies it could be demonstrated that glutamate antagonists, calcium antagonists or radical scavengers reduce the ischemic damage. Substances which interact with inflammation or apoptosis have also been shown to be protective. Clinical trials, however, showed no beneficial effects. This discrepancy is mainly due to differences in the design of the studies. In experimental studies the substances were often applied before or at the onset of ischemia, the survival time after ischemia was very short and the effects of neuroprotection were mainly evaluated by morphological examinations. Considering these points in future preclinical studies it is hoped that neuroprotective substances will be found which may be effective in clinical trials.