Neuronal apoptosis following cerebral ischaemia: pathophysiology and possible therapeutic implications.
OBJECTIVE
Neuronal apoptosis following cerebral ischaemia has become an issue of extraordinary scientific interest in the past decade. Besides necrosis, this highly relevant pathomechanism has been shown to be markedly involved in the pathogenesis of delayed postischaemic neuronal damage. As a result, a variety of possible neuroprotective strategies and therapeutic options subsequent to cerebral ischaemia have emerged. This article provides an overview of the pathophysiologic mechanisms underlying delayed neuronal apoptotic degeneration after cerebral ischaemia. Based on these facts, selected therapeutic implications are discussed in detail.


RESULTS
Recent findings from experimental studies have demonstrated a new therapeutic neuroprotective potential of pharmaceutical blockade of death-inducing ligands (e.g. Fas/CD95 ligand), enhancement of survival signal transduction with endogenous ligands (e.g. erythropoietin) and therapeutically modulating the balance between intracellular anti- and proapoptotic Bcl proteins with intriguing molecular techniques after cerebral ischaemia.


CONCLUSIONS
Neuronal apoptosis is highly relevant in the pathophysiology of neurodegenerative disorders, neurotrauma and cerebral ischaemia/reperfusion. Within the past few years, a variety of therapeutic strategies have emerged based on our increasing knowledge of the pathophysiology of apoptosis. Whereas inhibition of single factors in apoptotic cascades (e.g. proteases) has produced rather unsatisfying results, new opportunities have emerged at the molecular level due to advances in molecular medicine. These approaches offer promising opportunities for neuroprotective therapeutic strategies subsequent to cerebral ischaemia. It is tempting to speculate that a combination ('cocktail') of these antiapoptotic interventions might even increase their neuroprotective potential.
Padosch
Stephan A
SA
Department of Legal Medicine, University of Bonn, Bonn, Germany.
Böttiger
Bernd W
BW