Melatonin as an Antioxidant Agent in Stroke: An Updated Review

Abstract

Stroke is a devastating disease associated with high mortality and disability worldwide, and is generally classified as ischemic or hemorrhagic, which share certain similar pathophysiological processes. Oxidative stress is a critical factor involved in stroke-induced injury, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, brain edema, and neuronal death. To alleviate these serious secondary brain injuries, neuroprotective agents targeting oxidative stress inhibition may serve as a promising treatment strategy. Melatonin is a hormone secreted by the pineal gland, and has various properties, such as antioxidation, anti-inflammation, circadian rhythm modulation, and promotion of tissue regeneration. Numerous animal experiments studying stroke have confirmed that melatonin exerts considerable neuroprotective effects, partially via anti-oxidative stress. In this review, we introduce the possible role of melatonin as an antioxidant in the treatment of stroke based on the latest published studies of animal experiments and clinical research.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics

“…Moreover, the determinations of oxidative stress biomarkers presented in those studies are performed in a wide-time window or from blood serum collected only after the completion of thrombolytic therapy. The influence of initial markers of oxidative stress on the prognosis of intravenous thrombolytic therapy is unknown, although the authors of the publication raise the issue of the application of antioxidants in the treatment and prevention of stroke [ 17 ].…”

The Role of Potential Oxidative Biomarkers in the Prognosis of Acute Ischemic Stroke and the Exploration of Antioxidants as Possible Preventive and Treatment Options

“…Total Antioxidant Power (TAP) could evaluate the overall status of oxidative homeostasis by measuring the free radical-reducing capacity of all dietary non-enzymatic antioxidants (hydrophilic and lipophilic). Additionally, TAP could provide information about the synergistic effects between different antioxidants [ 49 , 181 , 186 , 187 ].…”

“…Moreover, the few available studies have provided contradictory observations with respect to TAP levels in AIS patients. For an instance, there are some studies that associated high TAP levels with the AIS incidence [ 49 , 186 ], whereas other studies have reported lower TAP levels for the same pathology [ 181 , 187 ], or no significant difference between the circulating TAP in AIS compared to controls [ 45 , 188 ]. Though the high TAP levels reported in acute ischemic stroke are seemingly creating confusion, Lorente et al [ 186 ] provided a plausible explanation by including the surviving and non-surviving ischemic stroke patient’s data in the statistical analysis.…”

“…As immediate intervention during a stroke is ethically necessary, relevant biomarkers of oxidative stress have been reported solely in blood samples collected following the thrombolytic therapy. Therefore, there is limited understanding regarding the role of these specific biomarkers in the events occurring just before or during a stroke event [ 21 , 48 , 49 ]. Furthermore, it was previously suggested that oxidative stress extent could compel prognosis and outcomes following an acute ischemic stroke related to cognitive impairments and mortality risk [ 49 ].…”

“…Therefore, there is limited understanding regarding the role of these specific biomarkers in the events occurring just before or during a stroke event [ 21 , 48 , 49 ]. Furthermore, it was previously suggested that oxidative stress extent could compel prognosis and outcomes following an acute ischemic stroke related to cognitive impairments and mortality risk [ 49 ]. For an instance, Wang et al [ 50 ] found that the correlation between oxidized LDL plasma levels and cognitive performance following stroke (as evaluated by Mini-Mental State Examination test) fit into a linear regression model.…”