Brain Edema: a Classification Based on Blood-brain Barrier Integrity

Brain edema is a frequent complication of a variety of brain injuries and disorders. Two primary types of brain edema can be distinguished depending upon the integrity of the blood-brain barrier. With intact-barrier edema, the permeability of the blood-brain barrier is normal and brain edema results from a disturbance in ionic homeostasis. This type of edema is typically associated with swelling of the brain cells and a contraction of the extracellular space. In open-barrier edema, the permeability of the blood-brain barrier is increased and brain edema results from the oncotic forces generated by an influx of serum proteins into brain. In this case, the edema fluid accumulates primarily in the extracellular space. To a greater or lesser extent, both types of edema occur simultaneously in the majority of clinical conditions; however, one form usually predominates and demands the attention of both the scientist and clinician. Furthermore, classification of brain edema based upon blood-brain barrier integrity is useful to focus research on common mechanisms for brain edema formation and to direct therapy. This review considers intact-barrier and open-barrier edema with regard to their (a) histological features, (b) biophysical forces, (c) possible biochemical mediators, (d) mechanisms of resolution, and (e) implications for therapy.