Antioxidant Therapies for Neuroprotection—A Review

Abstract

Although moderate concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are crucial for various physiological processes within the human body, their overproduction leads to oxidative stress, defined as the imbalance between the production and accumulation of ROS and the ability of the body to neutralize and eliminate them. In the brain, oxidative stress exhibits significant effects, due to its increased metabolical activity and limited cellular regeneration. Thus, oxidative stress is a major factor in the progressive loss of neurons structures and functions, leading to the development of severe neurodegenerative disorders. In this context, recent years have witnessed tremendous advancements in the field of antioxidant therapies, with a special emphasis for neuroprotection. The aim of this paper is to provide an overview of the oxidative stress and antioxidant defense mechanisms and to present the most recent studies on antioxidant therapies for neuroprotection.

Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms

“…The Nrf2 signalling pathway (nuclear factor E2) is the main cause of cellular defence against oxidative stress. The Nrf2 activates phase II detoxifying enzymes via antioxidant response element (ARE) regulation [ 74 ]. Antioxidant response element (ARE) also activates NF-kappa B inflammatory responses [ 69 ].…”

“…Glutathione, a tripeptide that produces glutathione monoethyl ester (GSHE) by reduction process, acts as an antioxidant in controlling apoptosis and retard ROS generation. The GSHE diminishes SC LPO generation and the glutamate excitotoxicity [ 74 ]. Omega-3 fatty acid (ω-3 PUFAs) and docosahexaenoic acid (DHA) possess anti-inflammatory, antioxidant and membrane-stabilising activity.…”

“…Omega-3 fatty acid (ω-3 PUFAs) and docosahexaenoic acid (DHA) possess anti-inflammatory, antioxidant and membrane-stabilising activity. ω-3 PUFAs and DHA act on cyclooxygenase (COX) pathways, cytosolic phospholipase A2 (cPLA2), and kappa-light-chain-enhancer (NF-kB) and inhibit the production of ROS, RNS and lipid peroxidation of nerve cells [ 74 ], promoting neuroprotective pathways ( Figure 6 ).…”

“…A high dose of MP causes LPO inhibition, whereas low doses promote anti-inflammatory and anti-oxidative activity. Although high doses of MP for acute SCI responses are previously recommended, new guideline by AANS and CNS (2013) has restricted MP use for acute SCI because this drug showed modest efficacy but also possible severe complications [ 74 , 77 ]. High-dose MP therapy is no longer routinely used in acute SCI but remains an optional therapeutic approach in certain conditions [ 74 ].…”

“…Although high doses of MP for acute SCI responses are previously recommended, new guideline by AANS and CNS (2013) has restricted MP use for acute SCI because this drug showed modest efficacy but also possible severe complications [ 74 , 77 ]. High-dose MP therapy is no longer routinely used in acute SCI but remains an optional therapeutic approach in certain conditions [ 74 ]. A recent guideline restricts the administration of 24 h infusion of high-dose MP within 8 h of acute SCI as a treatment option and did not recommend 48 h infusion of high-dose MP [ 77 ].…”