• The brain is a highly aerobic tissue, with oxygen rather than any other metabolic substrate serving as the limiting substance for energy production.
• As the oxygen tension within the cell decreases, there is loss of oxidative phosphorylation and decreased generation of ATP in the mitochondria.
• Intracellular ATP production becomes dependent on anaerobic glycolysis in the cytoplasm. This produces small quantities of ATP not sufficient to maintain cellular metabolism.

Each glucose molecule produces:

• In aerobic metabolism 36-38 ATP with oxidative phosphorylation in the mitochondria
• In anaerobic metabolism in hypoxic conditions 2 ATP and 2 molecules of lactic acid in the cytoplasm

• The activity of the plasma membrane energy-dependent sodium pump (Na+ , K+ -ATPase) is reduced.
• Failure of this active transport system causes sodium to accumulate intracellularly with diffusion of potassium out of the cell.
• The net gain of solute is accompanied by isosmotic gain of water resulting in cellular swelling.