How to repair an ischemic brain injury? Value of experimental models in search of answers

Abstract

The major aim of experimental models of cerebral ischemia is to study the cerebral ischemic damage under controlled and reproducible conditions. Experimental studies have been fundamental in the establishment of new concepts regarding the mechanisms underlying the ischemic brain injury, such as the ischemic penumbra, the reperfusion injury, the cell death or the importance of the damage induced on mitochondria, glial cells and white matter. Disagreement between experimental and clinical studies regarding the benefit of drugs to reduce or restore the cerebral ischemic damage has created a growing controversy about the clinical value of the experimental models of cerebral ischemia. One of the major explanations for the failure of the clinical trials is the reductionist approach of most therapies, which are focused on the known effect of a single molecule within a specific pathway of ischemic damage. This philosophy contrasts to the complex morphological design of the cerebral tissue and the complex cellular and molecular physiopathology underlying the ischemic brain injury. We believe that the main objective of studies carried out in experimental models of cerebral ischemic injury must be a better understanding of the fundamental mechanisms underlying progression of the ischemic injury. Clinical trials should not be considered if the benefit obtained in experimental studies is limited or weak.