Editors' ChoiceStroke

To Serve and Neuro-Protect

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Science Translational Medicine  30 May 2012:
Vol. 4, Issue 136, pp. 136ec93
DOI: 10.1126/scitranslmed.3004350

Stroke is a sudden and devastating event that leaves many patients with long-term disabilities. Although the mechanisms and risk factors for stroke have been well defined, there are few effective therapies for treating patients who have had a stroke. The only available drugs for reducing the damaging effects of stroke are fibrolytic agents that dissolve clots blocking arteries in the brain, but patients have to be treated with these drugs within a few hours in order for them to be effective. Although a number of neuroprotective compounds have been tested in clinical trials, none of them have been successful. Now, Cook et al. have identified a new compound that can preserve brain tissue and neural function in nonhuman primates after a severe stroke.

In stroke, disruption of the brain’s blood supply leads to the release of the neurotransmitter glutamate from nerve cells. Excess glutamate causes excitotoxicity in nerve cells by overstimulating them and is a major cause of brain damage after a stroke. Cook and colleagues first induced stroke in nonhuman primates through cerebral artery occlusion. They then treated the primates with placebo or an inhibitor of postsynaptic density protein 95 (PSD-95), a molecule that is crucial for glutamate-mediated excitotoxicity. The primates treated with the PSD-95 inhibitor had a 70% reduction in the size of the damaged region of the brain in comparison with the placebo control group. In addition, the treated primates showed improvements in a variety of neural functions in comparison with placebo-treated animals.

The study by Cook et al. shows that a PSD-95 inhibitor may be effective for treating stroke in nonhuman primates. Neuroprotective therapies have been notoriously difficult to translate from preclinical experiments in animal models to clinical treatments. Further studies are needed to see whether the drug reported by Cook et al. can bridge the gap from animal model to clinical care.

D. J. Cook et al., Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 483, 213–217 (2012). [Abstract]

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