Alternative methods of neuroprotection in brain ischemia

Learning of cellular and molecular mechanisms of the ischemic neuronal damage led to development of pharmacological methods of neuroprotection targeted at these mechanisms. They were effective in animal stroke models, but none of them passed clinical trials. Thus the alternative experimental neuroprotective strategies emerge. Preclinical studies demonstrated that mild hypothermia signifi cantly improves the outcome in the animal models of stroke and brain injury. This method of still unclear mechanism has been successfully used in specifi c clinical conditions and has been tested in several trials. It is hoped that moderate hypothermia soon may be introduced as an alternative method of stroke treatment. Ischemic preconditioning is a way of inducing tolerance to brain ischemia by preceding the injurious ischemia with the sub-lethal stressors like short ischemia, mild hypoxia, heating or pharmacological treatment. The exact mechanisms of activation and induction of brain tolerance to ischemia by preconditioning are not clear. Recently post-conditioning, i.e. neuroprotective effect of the post-treatment with sub-lethal stressors after injurious ischemia has been demonstrated, pointing to a therapeutic potential of such a treatment, still being tested at the preclinical level.