Brain edema in acute liver failure: Can it be prevented? Can it be treated?

A model to explain the development of brain edema. Circulating factors include hypo-osmolarity (as with hyponatremia), hyperammonemia and cytokines (which bind to endothelial cell receptors). The permeability of the blood-brain barrier is presumed intact, though this has been recently questioned [4]. Water movement into astrocytes may proceed via specialized pores, including aquaporin-4 (Aq4) in the endothelium and astrocyte plasma membrane. The generation of glutamine (GLN) within astrocytes from the amidation of glutamate (GLU), a reaction catalyzed by glutamine synthetase (GS), results in cellular swelling as a result of osmotic [10] and/or non-osmotic [11] effects. A net consequence of the processes that lead to swelling is the generation of oxidative and nitrosative stress within glial cells, a mechanism involved in the induction of cerebral hyperemia. The latter is critical for the net gain in water that is needed to result in brain edema [35]. Most of the elements of this model originate from studies in rats with ammonia-induced brain edema, a model where the development of brain swelling can be studied independently from the extent of liver failure.