Improvement of a Novel Proposal for Antioxidant Treatment Against Brain Damage Occurring in Ischemic Stroke Patients

Abstract

: The underlying mechanism of cerebral injury occurring in patients with acute ischemic stroke involves a key pathophysiological role of oxidative stress. Thus, reactive oxygen species are related to the development of brain edema, calcium overload, mitochondrial dysfunction, excitotoxicity, iron release and inflammation. Nevertheless, although experimental studies have tested the use of antioxidants as an adjuvant therapy in this setting, clinical data and randomized trials are still lacking. Current approved pharmacological therapy is aimed at reperfusion strategies; however, the therapeutic window is limited and also challenged by the injury known to result from the reperfusion. We have recently defined a timecourse occurrence of pathological events triggered by reperfusion-dependent increased reactive oxygen species, thus suggesting the beneficial role of the pertinent use of antioxidants. The present study was aimed to support the hypothesis that an enhanced antioxidant neuroprotection could be achieved by the use of two or more antioxidants opportunely provided to ischemic stroke patients focused against the specific mechanism occurring throughout the pathophysiological process. From this paradigm,using an underexplored therapeutic principle, it could be suggested that antioxidant-based therapy is a novel, promising, safe, available and cost-effective strategy against the deleterious effects of ischemic stroke that needs to be further studied in clinical protocols.

Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?

“…It is suggested that oxidative stress may be one of the mechanisms inducing ferroptosis in cerebral stroke. During IR, neuronal cells in the penumbra may be subjected to oxidative stress caused by pro-oxidants ROS and reactive nitrogen species (RNS) ( Orellana-Urzúa et al, 2021 ). ROS comprise free radicals such as ·OH and superoxide (O 2 − ) as well as some nonradical molecules such as H 2 O 2 , whereas commonly observed RNS are nitric oxide (NO·) and peroxynitrite (ONOO − ) ( Prasad et al, 2019 ).…”

Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

“…The opposite process would be an increase in the generation of free radicals, which can happen through intracellular mitochondrial dysfunction, or through an extracellular source such as inflammation, as discussed above. The time-course of oxidative stress is initially mitochondria-mediated, for example, due to oxygen and glucose deprivation and following mitochondrial depolarization, and is then xanthine oxidase-mediated, NOS-induced and later NADPH oxidase-mediated [ 20 ].…”

“…In stroke, the results of ROS imbalance are considerable and include apoptosis, blood-brain barrier (BBB) disruption, inflammation, edema formation, autophagy and other pathophysiological events [ 20 ]. ROS and RNS are generated mainly by microglia and astrocytes [ 28 ].…”

Effectively Improve Ischemic Stroke’s Strategy: Attenuate Oxidative Stress

“…The basic cause of neurological impairment caused by IS is a brain injury of nerve cell death or apoptosis, acute phase for brain energy metabolism disorder caused by glucose and oxygen supply and oxygen free radical formation, nerve cells Ca2+ overload, the formation of excitatory amino acids and noninfectious inflammatory reaction, resulting in a large number of nerve cell necrosis and apoptosis, causes corresponding neurological defects, including hemiplegia, motor, sensory, language dysfunction, etc. [4,5]. What's more, cerebral embolism induced by nerve damage or vascular blockage caused by hypoxia is the leading cause of IS, and oxidative stress, inflammatory, and blood-brain barrier failure play a huge role in this process [6].…”