Neuroprotection in Acute Stroke: Is There Still Hope?

Efficacious treatment of acute stroke is a major challenge in modern medicine. Therapeutic neuroprotection acting towards minimization of ischemic neuronal injury in penumbral tissue in the regions of reduced cerebral blood flow seems to be an appealing concept in the treatment of acute stroke and brain trauma. The ‘ischemic cascade’, a complex mechanism of metabolic events initiated by brain ischemia, offers many pathways by which the neuroprotective agents may act. Time to treatment remains a major limiting factor for many potential neuroprotective agents. Although the exact therapeutic window is not known, evidence from many animal models and clinical research suggest that neuroprotective therapy can only be efficacious if administered very early after the onset of ischemia. Various neuroprotective agents have been tested in many clinical stroke trials during the past 20 years. Large phase III clinical trials of several classes of neuroprotectants (mainly NMDA receptor antagonists, free radical scavengers, and calcium channel blockers) have recently failed to demonstrate efficacy of neuroprotection. After initial disappointment, the active research continues and some new exciting neuroprotective models emerge on the horizon.