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Brain Edema in Neurological Disease 155 methylprednisolone. Treatment with 1 g/day of methylprednisolone for 3–5 days reduces the inflammatory changes in the blood vessels during an acute exacerbation. Dramatic reduction in enhancement on MRI may be seen after treatment. However, the effect is lost after several months. High-dose steroids reduce the MMP-9 in the brain as reflected in the CSF, preserving the integrity of the BBB (Rosenberg et al., 1996b). Treatment of edema surrounding an intracerebral hemorrhage has recently been intensively studied because of the side-effect of hemorrhagic transformation in patients treated with tPA. As in studies of edema s econdary to ischemia, a large number of animal studies have documented the use of various agents to reduce the edema secondary to the hemorrhage. One promising study using recombinant acti- vated factor VII reduced growth of the hemorrhage in an initial study (Mayer et al., 2005). A subsequent study failed to confirm the results of the first because of a high rate of thrombotic complications (Mayer et al., 2008). Several other studies are underway, including stereotactic removal of the clot that has been dissolved with intraventricular tPA, but results are not available for this study. 11 Conclusions Cerebral edema is common in many neurological disorders. When the metabolism of the cell fails, the cells are unable to remove sodium and the cells swell. This is seen on MRI as an area of restricted diffusion. Alternatively, the blood vessels may be damaged as part of an injury, infection, or autoimmune process, resulting in vaso- genic edema, which has a predilection for the white matter. Common mechanisms involved in cellular swelling include failure of membrane ion pumps, retention of sodium inside the cell, and increases in intracellular calcium, initiating an inflam- matory response. Proteases and free radicals degrade extracellular matrix and tight junction proteins leading to vascular edema and hemorrhage. An important advance in our understanding of brain edema was made with the discovery of AQPs, which were shown to be located in astrocyte endfeet and water-controlling surfaces of the brain. Although knowledge of the mechanisms of brain edema continues to grow, the challenge remains the translation of that information into treatments. Acknowledgments This work was supported by grants from the National Institutes of Health (NIH) to GAR (R01 NS045847 and R01 NS052305). References Abbott NJ (2004) Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int 45:545–552 Abbruscato TJ, Davis TP (1999) Protein expression of brain endothelial cell E-cadherin after hypoxia/aglycemia: influence of astrocyte contact. 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