Lost in translation: taking neuroprotection from animal models to clinical trials.
Caffeinol has been proposed as a neuroprotectant for human trials. This review covers a variety of animal models used and various attempts to take animal protocols to human trials. The accompanying paper discusses the rabbit model that was used to identify the efficacy of tissue plasminogen activator (tPA) treatment. To date, this is the only model that was able to achieve laboratory to clinical translational success. Use of caffeinol as a cytoprotective agent in rat models yielded exciting results, which led to clinical trials. However, caffeinol given with tPA in rabbits leads to increased hemorrhage. Caffeinol alone does not prove to be neuroprotective, as vasodilation by itself is not efficacious. However, vasodilation combined with thrombolysis (caffeinol with tPA) poses an increased risk of hemorrhage. For a more translational approach to study neuroprotection and neuroprotective agents in human trials, it is necessary to demonstrate the efficacy of the procedure and purported agents in several animal models.
Hoyte
L
L
Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, AB, Canada T2N 2T8.
Kaur
J
J
Buchan
A M
AM
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002110:Caffeine / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D002110:Caffeine; D000431:Ethanol; D010959:Tissue Plasminogen Activator