ABSTRACT
Although the brain is only 2% of the total body mass, it receives 20% of the cardiac output and requires a constant supply of oxygen and glucose, so the energy needs are seven times higher than in other organs. Pathogenesis of ischemic brain damage involves three phases: ischemic depolarization (ID), biochemical cascade, and reperfusion damage. ID leads to interruption of oxygen and glucose supply, resulting in conversion to anaerobic metabolism and accumulation of lactic acid. A few minutes after the arrest, neuronal electrical activity stops and energy loss and ionic homeostasis damage occur. Metabolic imbalance affects mitochondria and endoplasmic reticulum, which contain Ca2+ ion channels. When Ca2+ ions massively accumulate in the mitochondria, they disable the function of the mitochondria and lead to a decrease in the production of adenosine triphosphate (ATP) and the creation of reactive oxygen species (ROS). At the same time, inflammatory processes are activated by infiltration of neutrophils into the damaged tissue. After the ischemic process, microglia are rapidly activated, and activated microglia release high levels of IL-23 1 day after ischemic reperfusion and lead to infiltration of γδ T lymphocytes into the brain, thereby exacerbating brain damage.
