Nitroxyl in the central nervous system.

Nitroxyl (HNO) is the one-electron-reduced and protonated congener of nitric oxide (NO). Compared to NO, it is far more reactive with thiol groups either in proteins or in small antioxidant molecules either converting those into sulfinamides or inducing disulfide bond formation. HNO might mediate cytoprotective changes of protein function through thiol modifications. However, HNO is a strong oxidant that in vitro reacts with glutathione to form glutathione disulfide and glutathione sulfinamide. The resulting oxidative stress might aggravate tissue damage in inflammatory diseases. In this review, we will summarize the current knowledge of how exogenous HNO affects the central nervous system, especially nerve cells and glia in health and disease. Unlike most other organs, the brain is separated from the circulation by the blood-brain barrier, which limits access of many pharmacological compounds. Given that, we will review what is known about the ability of currently used HNO donors to cross the blood-brain barrier. Moreover, considering that the physiology and composition of the brain has unique properties, for example, expression of brain-specific enzymes like neuronal NO synthase, its high iron content, and increased energy metabolism, we will discuss possible sources of endogenous HNO in the brain.