Inadequate Energy Supply

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Lack of glucose and oxygen deplete the cellular energy stores required to maintain electrical potentials and ion gradients.

In ischemic brain tissue, the membrane that surrounds each affected neuron becomes “leaky,” and the cell loses potassium and adenosine triphosphate (ATP), the tissue’s medium for energy exchange.

Energy failure is not the immediate cause of cell death, however, since all brain cells tolerate loss of ATP for several minutes. In humans, it appears that 5 to 10 minutes of complete occlusion is required for irreversible brain damage. In actuality, most strokes do not involve a complete occlusion of blood flow, but even a partial occlusion, if allowed to continue for a sufficient time, may produce irreversible brain damage.

Once blood flow to cerebral neurons diminishes, one or more branching mechanisms may independently lead to brain cell death. These mechanisms may involve deterioration of ion gradients or the effects of anaerobic metabolism.

With respect to the latter, anaerobic glycotic pathways are utilized in the affected region to compensate for the loss of oxygen and provide a source of energy. However, this produces damaging byproducts, including lactic acid and hydrogen ions, which accumulate in tissue in proportion to the carbohydrate stores present at the outset of ischemia. Toxicity of hydrogen ions, especially their ability to facilitate ferrous-iron-mediated free-radical mechanisms, appears to irreversibly affect neuronal integrity.

Acute Ischemic Stroke: New Concepts of Care
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