Neuroprotection Does Not Work!

For more than 2 decades neurologists have searched for a drug that protects ischemic brain tissue from cell death—without success so far. The list of drugs tested in phase II and III trials is long. One of the first substances that showed a neuroprotective effect in experimental ischemia was the NMDA-antagonist MK-801,1 which protected hippocampal CA1 and CA2 pyramidal neurons. Besides NMDA antagonists, other neuroprotective agents such as radical scavengers, calcium antagonists, sodium, or potassium channel blockers, cell membrane stabilizers, antiinflammatory agents, antiadhesion molecules, glycine-, AMPA-, and serotonin-receptor antagonists significantly reduced the infarct volume in animal models but were disappointing in clinical trials. Side effects, especially drowsiness and impaired consciousness, limited the clinical application in some agents. Surrogate markers such as stroke MRI was applied to support proof of principle that infarct growth was prevented or reduced. But neither the infarct volume nor clinical outcome was influenced persuasively.Many arguments may be …