Role of Nitric Oxide Signaling Pathways in Brain Injuries

Maria      Aurelia Zorrilla-Zubilete; Damian      Gustavo Maur; Maria      Laura Palumbo; Ana      Maria Genaro

Abstract

Nitric oxide (NO) is involved in many physiological and pathological brain processes. NO is probably the smallest and most versatile bioactive molecule identified. NO signaling in excitable tissues requires rapid and controlled delivery of NO to specific cellular targets. This tight control of NO signaling is largely regulated at the level of its biosynthesis. NO production might lead either to toxicity or to neuroprotection depending on the level of NO, the location of NO production, the extent of oxidative stress and the type of neurodegenerative process. It has been suggested that NO directly acts as an antioxidant. This protective effect is mediated by small fluxes of NO ( < 1 μmol/L). This is consistent with the fact that NO terminates lipid peroxidation reactions and suggests that the production of NO is a major protective mechanism against oxidative stress in vivo. In fact it has been demonstrated, in vitro as well as in vivo, that during brain insult NO might be part of the physiological response to injury. In general, it is accepted that a normal pathophysiologic response of the damaged tissue may involve controlled NO production and the inhibition of this response may interfere with the normal repair process. Nevertheless, it has been suggested that a high production of NO after the induction of iNOS expression can interact with superoxide anion generated by the mitochondria or by other mechanisms, leading to the formation of the potent oxidant species peroxynitrite. These events would result in cell damage and altered neuronal physiological function. The present review focuses on the role of NO as an important neuromodulator that can exert both neurotoxic and neuroprotective effects in different injuries.

Keywords: Brain injuries, chronic stress, intracellular signaling, neurotoxicity, neuroprotection, nitric oxide

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