The failure of animal models of neuroprotection in acute ischemic stroke to translate to clinical efficacy.

Abstract

The discrepancy in results regarding neuroprotective agents in animal experiments compared to clinical trials is a major problem. While many neuroprotective agents have been proven effective in a variety of animal ischemic stroke models, none have been shown to work in phase III clinical trials. This review retrospectively summarizes the neuroprotectants selected for human randomized controlled trials (RCT) and explores the reasons behind the clinical translational failure of these agents. Here, we suggest that there are many factors (model selection, anesthetic choice, physiological monitoring, model success criteria, embolus property, reperfusion damage, infarction area, therapeutic time window, drug penetration, blood concentration, gender difference, and outcome evaluation) responsible for this phenomenon. Ultra-early treatment using a "home run" drug and multi-target therapy may be the most promising for future consideration.

• Authors: Sui-Yi Xu, Su-Yue Pan
• Journal: Medical science monitor basic research (Med Sci Monit Basic Res) Vol. 19 Pg. 37-45 (Jan 28 2013) ISSN: 2325-4416 [Electronic] United States
• PMID: 23353570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Neuroprotective Agents

Topics

• Animals
• Brain Ischemia (complications, drug therapy)
• Disease Models, Animal
• Humans
• Neuroprotective Agents (therapeutic use)
• Stroke (complications, drug therapy)
• Translational Research, Biomedical
• Treatment Outcome