Marek Furman1, Miroslava Nemethova1, Lubica Macakova1, Vladimir Sihotsky2, Ivan Kopolovets3, Peter Berek3, Michal Virag3, Rastislav Mucha1. 1. Institute of Neurobiology of Biomedical Research Center, Slovak Academy of Sciences, Soltesovej 4, 040 01, Kosice, Slovakia. 2. Eastern Slovak Institute of Cardiovascular Diseases and Faculty of Medicine, Pavol Jozef Safarik University, Ondavska 8, 040 01, Kosice, Slovakia. vsihotsky@vusch.sk. 3. Eastern Slovak Institute of Cardiovascular Diseases and Faculty of Medicine, Pavol Jozef Safarik University, Ondavska 8, 040 01, Kosice, Slovakia.
Abstract
BACKGROUND: A stroke is an acute damage to a certain area of a nerve tissue of the brain. In developed countries, it ranks second among the most often causes of death and is also the leading cause of disability. Recent findings emphasize the significant neuroprotective effect of conditioning on the course and rate of recovery after ischemic attack; however the molecular mechanism of ischemic tolerance induced by conditioning is still not completely explored. METHODS AND RESULTS: The purpose of this study is an identification of changes in gene expression induced by stimulation of reaction cascades after activation of the neuroprotective mechanism using an experimental rat model of global ischemia. The induction of neuroprotective cascades was stimulated by the application of early and delayed form of remote ischemic postconditioning. The quantitative qRT-PCR method was used to assess the rate of change in ADM, BDNF, CDKN1A, CREB, GADD45G, IL6, nNOS, and TM4SF1 gene expression levels 72 h after ischemic attack. The detected results confirm the neuroprotective effect of both forms of postconditioning. Participation of neuroprotection-related gene expression changes was observed once as an early one (CREB, GADD45G), once as a delayed one (ADM, IL6), or both (BDNF, CDKN1A, nNOS, TM4SF1) postconditioning forms, depending on the particular gene. CONCLUSIONS: Our results characterize impact of ischemic tolerance on the molecular level. We predict ischemic tolerance to be consisted of complex combination of early and delayed remote postconditioning.
BACKGROUND: A stroke is an acute damage to a certain area of a nerve tissue of the brain. In developed countries, it ranks second among the most often causes of death and is also the leading cause of disability. Recent findings emphasize the significant neuroprotective effect of conditioning on the course and rate of recovery after ischemic attack; however the molecular mechanism of ischemic tolerance induced by conditioning is still not completely explored. METHODS AND RESULTS: The purpose of this study is an identification of changes in gene expression induced by stimulation of reaction cascades after activation of the neuroprotective mechanism using an experimental rat model of global ischemia. The induction of neuroprotective cascades was stimulated by the application of early and delayed form of remote ischemic postconditioning. The quantitative qRT-PCR method was used to assess the rate of change in ADM, BDNF, CDKN1A, CREB, GADD45G, IL6, nNOS, and TM4SF1 gene expression levels 72 h after ischemic attack. The detected results confirm the neuroprotective effect of both forms of postconditioning. Participation of neuroprotection-related gene expression changes was observed once as an early one (CREB, GADD45G), once as a delayed one (ADM, IL6), or both (BDNF, CDKN1A, nNOS, TM4SF1) postconditioning forms, depending on the particular gene. CONCLUSIONS: Our results characterize impact of ischemic tolerance on the molecular level. We predict ischemic tolerance to be consisted of complex combination of early and delayed remote postconditioning.