Format

Send to

Choose Destination
Stroke. 2009 Mar;40(3 Suppl):S111-4. doi: 10.1161/STROKEAHA.108.528877. Epub 2008 Dec 8.

Current status of neuroprotection for cerebral ischemia: synoptic overview.

Author information

1
Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, FL 33101, USA. mginsberg@med.miami.edu

Abstract

Abundant preclinical studies have identified multiple mechanisms of ischemic brain injury and have provided proof of principle that strategies designed to counter these mechanisms can protect the ischemic brain. This review article emphasizes the translation of these strategies from the laboratory to clinical trials. It is a disappointing fact that many agents have been brought to clinical trial despite only modest or inconsistent preclinical evidence of neuroprotective efficacy. Preclinical investigations require rigorous attention to a variety of variables that may influence outcome. The widely touted STAIR criteria represent constructive guidelines for preclinical testing but, as experience has shown, do not increase the likelihood of translational success. Of the approximately 160 clinical trials of neuroprotection for ischemic stroke conducted as of late 2007, only approximately 40 represent larger-phase completed trials, and fully one half of the latter utilized a window to treatment of >6 hours, despite strong preclinical evidence that this delay exceeds the likely therapeutic window of efficacy in acute stroke. Other shortcomings of these trials include the use of agents lacking robust, consistent preclinical efficacy; inability to achieve adequate dosing in humans; and suboptimal clinical and statistical design features. Taken together, these factors identify areas of needed improvement for future trials.

PMID:
19064810
PMCID:
PMC2697575
DOI:
10.1161/STROKEAHA.108.528877
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center