Oxidative Stress at the Crossroads of Aging, Stroke and Depression

Abstract

Epidemiologic studies have shown that in the aging society, a person dies from stroke every 3 minutes and 42 seconds, and vast numbers of people experience depression around the globe. The high prevalence and disability rates of stroke and depression introduce enormous challenges to public health. Accumulating evidence reveals that stroke is tightly associated with depression, and both diseases are linked to oxidative stress (OS). This review summarizes the mechanisms of OS and OS-mediated pathological processes, such as inflammation, apoptosis, and the microbial-gut-brain axis in stroke and depression. Pathological changes can lead to neuronal cell death, neurological deficits, and brain injury through DNA damage and the oxidation of lipids and proteins, which exacerbate the development of these two disorders. Additionally, aging accelerates the progression of stroke and depression by overactive OS and reduced antioxidant defenses. This review also discusses the efficacy and safety of several antioxidants and antidepressants in stroke and depression. Herein, we propose a crosstalk between OS, aging, stroke, and depression, and provide potential therapeutic strategies for the treatment of stroke and depression.

The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases

“…In vascular inefficiency, ROS and reactive nitrogen species (RNS) cause an increased concentration of H+ and H 2 O 2 , leading to DNA injury, endothelial alteration, and mitochondrial dysfunction [ 390 ]. Moreover, this is worsened by damage through ROS-mediated inflammation, apoptosis, autophagy, and the microbial-gut-brain axis [ 390 ]. The depletion of energy in ischemic stroke can cause a series of injuries to promote the progress or recurrence of stroke, and OS is involved in all phases of ischemic stroke evolution.…”

“…Then, ROS increases vasoconstriction and triggers platelet aggregation and endothelial cell permeability, affecting blood circulation [ 391 ]. Additionally, RNS plays a role in mitochondrial functions, for instance, by reducing DNA and suppressing enzymes of the mitochondria [ 390 ]. Finally, ROS and RNS bring about DNA damage, protein destruction, lipid peroxidation, and cell death, leading to poor outcomes [ 390 , 392 ].…”

“…Additionally, RNS plays a role in mitochondrial functions, for instance, by reducing DNA and suppressing enzymes of the mitochondria [ 390 ]. Finally, ROS and RNS bring about DNA damage, protein destruction, lipid peroxidation, and cell death, leading to poor outcomes [ 390 , 392 ]. As expected, the results of clinical studies have confirmed that higher plasma levels of oxidized low-density lipoprotein led to a worse prognosis [ 393 ], an increased risk of death [ 394 ] and a higher prevalence of cognitive impairment [ 395 ].…”

“…Finally, there are important molecular and signaling pathways modifications with aging [ 390 ]. Under ischemia/hypoxia conditions in the elderly, Sirt1 expression and the mitochondrial unfolded protein response decrease in aging, leading to poor mitochondrial function and fitness [ 396 ].…”

“…In summary, OS has a central role in the “aging-stroke” system. First, when a stroke occurs in animals or patients, there is an excessive generation of ROS, causing cellular damage and brain injury [ 390 ]. Second, OS mediates inflammation, apoptosis, and the microbiota-gut-brain axis to increase the accumulation of ROS, followed by brain alteration [ 390 ].…”