Oxidative Stress as a Commonality Between Mechanisms of Stroke and Depression
Cells in aged tissue are characterized by a state of oxidative stress, the presence of excessive numbers of oxidizing molecules that damage cell structures by reacting with them. Oxidative stress goes hand in hand with chronic inflammation and mitochondrial dysfunction, both of which are also features of aged tissues. For any universal state of this nature, one can then link it to many varied conditions, even those that might initially appear to have very little to do with one another. That is the case here in this consideration of commonalities between depression and stroke.
A significant percentage of older individuals develop one or more age-related diseases, which may include two leading diseases characterized by high incidence and disability: stroke and depression. Between 2006 and 2016, the actual number of stroke deaths increased 3.7%, although the age-adjusted mortality rate decreased 16.7% due to the large increase in the number of elderly people. Like stroke, another disease that affects a significant proportion of the population is depression. The 12-month prevalence of major depressive disorder (MDD) is about 6%, while the lifetime risk of MDD is nearly 15-18%. Moreover, older age is identified as a consistent and important risk factor for a worse prognosis. This phenomenon may be associated with the effect of cognitive impairment.
Over the past two decades, studies have identified the role of oxidative stress (OS) in these two diseases. Recently, preclinical experiments and clinical trials have focused on studying the efficacy of antioxidants and combined therapy with antidepressants in stroke or depressed patients. OS describes a state in which the body produces excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) in response to deleterious substances. Under physiological conditions, moderate OS activity is necessary for body health. Toxic effects derived from ROS and RNS can be ameliorated or neutralized by free radical (FR) scavengers and the antioxidant system. However, when a large number of ROS and RNS are generated, excessive FR then induce molecular oxidation, cell membrane modification, and enzyme inactivation, resulting in cellular damage and functional decline.
There is a close link between oxidative stress and aging, and this link can be proven through many related mechanisms. Firstly, age-related cognitive decline is a consequence of increased OS and neuroinflammation activity in the the aging hippocampus, and a consequence of reduced neurogenesis and synaptic plasticity. Furthermore, mutual effects of inflammation and OS are observed to exacerbate the aging brain. Inflammation stimulates both macrophages and microglia to generate mitochondrial ROS to cause cognitive decline, whereas OS-damaged cells produce inflammatory mediators to promote microglial aging. Secondly, aging and OS can damage the brain by negatively affecting neuroplasticity, brain homeostasis, and cognitive function.
OS lies in the center of the "aging-stroke-depression" network. First, when stroke occurs in animals or patients, excessive generation of ROS follows, leading to cellular damage and brain injury. Second, OS mediates inflammation, apoptosis, and the microbiota-gut-brain axis to increase the accumulation of ROS, followed by brain deterioration. Third, aging acts as a risk factor and aggravates the development of stroke and depression via OS and OS-induced pathways. Due to the central role of OS in this network, administration of antioxidants seems to provide therapeutic ways for stroke and depression.