Brain acute ischemia mechanisms: implications to experimental and clinical treatment

Abstract

We have reviewed current understanding of ischemic brain damage and the main therapeutic approaches. Pathological factors affecting the survival of neurons and glial cells in the focus of ischemia are outlined: depolarization, cytotoxic and vasogenic edema, calcium overload, excitotoxicity, inflammation, free radical damage. Effective and rapid reperfusion significantly improves patient’s survival and functional outcomes, but other approaches to brain infarction treatment did not approve their effectiveness in large clinical trials. Dozens of drugs (neuroprotectors) are being studied in order to compensate isolated pathological brain ischemia pathways and to increase cellular survival, but they were ineffective in large clinical trials.The reason for the ineffectiveness of neuroprotective drugs may be a lack of understanding of the drug targets real importance. Many drugs that have shown promising results in preclinical studies have not been studied in large clinical trials until now. Additional pathogenetic mechanisms revealed in the last decade expand our knowledge about the brain infarction and may become promising directions for the development of new therapeutic approaches.