The brain operates by concentrating potassium inside the cells and sodium outside the cells. This ionic gradient maintains minute differences in electrical potential between the inside and outside of cells. This gradient allows for the generation of electrical signals essential for communication between the different parts of the brain. During ischemia, this gradient is damaged, since there is no energy to maintain the differences in the concentrations of sodium and potassium across the membrane. As a result, neurons depolarize and liberate neurotransmitters.
Neurons are more vulnerable than astrocytes or endothelial cells to ischemia.
They first undergo mitochondrial swelling and cristae disorganization, forming microvacuoles in the cytoplasm as a result. With a decreasing supply of oxygen and glucose, mitochondrial metabolism is severely impaired. Accumulation of waste products leads to damage Lactic acid accumulates since the interruption in blood flow prevents the removal of wastes. Acidosis is extremely toxic to brain cells, preventing normal cellular activities such as the restoration of mitochondrial function. Furthermore, acidosis promotes free radical formation and swelling in glial and endothelial cells.