Focusing on the protective effects of metallothionein-I/II in cerebral ischemia

Abstract

Ischemic stroke is a leading cause of death and has a remarkable social and economical impact, which rises with the increasing age of the industrial population. Unfortunately, treatment strategies for cerebral ischemia still remain very limited. Acute reperfusion therapies with either systemic thrombolysis using rt-PA (recombinant tissue plasminogen activator) or interventional recanalization procedures were shown to be highly effective. In addition, there is also a long-existing concept to modulate stroke-associated pathophysiological events such as exitotoxicity, peri-infarct depolarizations, apoptosis and inflammation (Dirnagl et al., 1999). Various such neuroprotective treatment regimes were also shown to be highly successful in rodent stroke models and were shown to reduce the ischemic injury and improve the neurological outcome. In contrast to that, almost all of these successful neuroprotective experimental stroke strategies failed in clinical studies. Current attempts to explain the frustrating failure to translate the promising experimental data to the human patients were based on limited group numbers in experimental studies, publication bias, or hypothesis-driven research approaches. Thus, there is an urgent need to extend pre-clinical studies before further human studies are initiated.