Cerebral edema causes intracranial hypertension (ICH) which leads to severe outcome of
patients in the clinical setting. Effective anti-edema therapy may significantly decrease the mortality in
a variety of neurological conditions. At present drug treatment is a cornerstone in the management of
cerebral edema. Osmotherapy has been the mainstay of pharmacologic therapy. Mannitol and
hypertonic saline (HS) are the most commonly used osmotic agents. The relative safety and efficacy
of HS and mannitol in the treatment of cerebral edema and reduction of enhanced ICP have been demonstrated in the past
decades. Apart from its osmotic force, HS exerts anti-edema effects partly through inhibition of Na+-K+-2Cl-
Cotransporter-1 (NKCC1) and aquaporin 4 (AQP4) expression in astrocytes. Melatonin may also reduce brain edema and
exert neuroprotective effect on several central nervous system diseases through inhibition of inflammatory response. The
inhibitors of Na/H exchanger, NKCC and AQP4 may attenuate brain edema formation through inhibition of excessive
transportation of ion and water from blood into the cerebral tissue. In this review we survey some of the most recent
findings in the drug treatment of brain edema focusing on the use of osmotherapy, melatonin and inhibitors of ion
cotransporters and water channels. A better understanding of the molecular mechanism of these agents would help to
improve in the clinical management of patients with brain edema.
Keywords: AQP4 inhibitor, bumetanide, cerebral edema, hypertonic saline, mannitol, melatonin, Na/H exchanger inhibitor.
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