Edema Formation

Ischemic brain edema is a combination of two major types of edema: cytotoxic (cellular) and vasogenic [Fishman RA. Cerebrospinal Fluid in Diseases in the Nervous System. 2nd Ed. Philadelphia, PA: W.B. Saunders Co; 1992:103-155]. Cytotoxic edema evolves over minutes to hours and may be reversible, while the vasogenic phase occurs over hours to days, and is considered an irreversibly damaging process.

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Cytotoxic edema is characterized by swelling of all the cellular elements of the brain (shown). In the presence of acute cerebral ischemia, neurons, glia (indicated by astrocytes), and endothelial cells swell within minutes of hypoxia due to failure of ATP-dependent ion (sodium and calcium) transport. With the rapid accumulation of sodium within cells, water follows to maintain osmotic equilibrium. Increased intracellular calcium activates phospholipases and the release of arachidonic acid, leading to the release of oxygen-derived free radicals and infarction.

Vasogenic edema (not shown) is characterized by an increase in extracellular fluid volume due to increased permeability of brain capillary endothelial cells to macromolecular serum proteins (e.g., albumin). Normally, the entry of plasma protein-containing fluid into the extracellular space is limited by tight endothelial cell junctions, but in the presence of massive injury, there is increased permeability of brain capillary endothelial cells to large molecules. Vasogenic edema can displace the brain hemisphere and, when severe, lead to cerebral herniation.

Acute hypoxia initially causes cytotoxic edema, followed within the next hours to days by the development of vasogenic edema as infarction develops (Fishman, 1992). The delayed onset of vasogenic edema suggests that time is needed for the defects in endothelial cell function and permeability to develop.

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