Oxidative Stress: A Major Player in Cerebrovascular Alterations Associated to Neurodegenerative Events

Abstract

The brain is one of the most exquisite organs in the body with high metabolic demands, and requires a tight regulation of the surrounding environment. This tight control is exerted by the neurovascular unit (NVU) comprising different cell types, where endothelial cells play the commander-in-chief role. Thus, it is assumable that even slight perturbations in NVU might affect, in some cases irreversibly, brain homeostasis and health. In this line, recent findings support the two-hit vascular hypothesis for neurodegenerative conditions, where vascular dysfunction underlies the development of neurodegenerative diseases, such as Alzheimer’s disease (AD). Knowing that endothelial cells are rich in mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, two major reactive oxygen species (ROS) sources, this review aims to gather information on how oxidative stress is in the front line of vascular alterations observed in brain aging and neurodegenerative conditions, particularly AD. Also, a brief discussion about the therapeutic strategies aimed to protect against cerebrovascular diseases is included.

Role of brain renin angiotensin system in neurodegeneration: An update

“…However, in a disease state, the integrity of this barrier may be affected, allowing hormonal RAS components entry into the cerebral regions, especially the cardiovascular regulatory areas (Palmer et al, 2013). Studies have shown that brain RAS triggers chronic inflammation leading to the release of ROS and inflammatory mediators through activating glial cells (Carvalho and Moreira, 2018). Uncontrolled effects of these mediators upregulate various inflammatory cascades resulting in cognitive dysfunction and neurodegeneration (Sun et al, 2018;Martire et al, 2015).…”

“…In a recent review, O'Connor and colleagues reported that excessive ang II generated due to astrocyte dysfunction resulted in neuroinflammation and loss of neuronal activity (Amin et al, 2016). In Addition, inflammation and other abnormal neurovascular alterations resulting from the effect of RAS along the AT1R axis have been linked to AD, although detailed mechanisms are still elusive (Carvalho and Moreira, 2018). Ang II treatment of mesencephalic cultures, caused activation of the microglial RhoA/ROCK pathway and the upregulation of microglia tumor necrotic factor, TNF a, a proinflammatory cytokine that facilitate dopaminergic neurodegeneration Saavedra, 2012).…”

Sodium tanshinone IIA sulfonate protects against Aβ‐induced cell toxicity through regulating Aβ process

“…Oxidative, nitrosative stress and inflammation in neuron can cause dysfunction of neural junction, and then induce the nervous system damage. 36 The antioxidant enzymes were significantly decreased in AD mice. 37,38 In this study, the primary indicators of oxidative and nitrosative stress were obviously increased after IL-1β, IL-6 and TNF-α, were observed in AD brain.…”

“…Oxidative, nitrosative stress and inflammation are playing crucial roles in cell homeostasis and apoptosis. Oxidative, nitrosative stress and inflammation in neuron can cause dysfunction of neural junction, and then induce the nervous system damage . The antioxidant enzymes were significantly decreased in AD mice .…”

The Potential for Natural Antioxidant Supplementation in the Early Stages of Neurodegenerative Disorders

“…The blood-brain barrier (BBB) neuro vascular unit (NVU), made up of neurons, astrocytes, pericytes, microglia and endothelial cells, can counteract the effects of oxidation when the amount of ROS is limited and when the activity of antioxidant enzymes is preserved. Any imbalance in the NVU functioning may alter the brain homeostasis, resulting in high oxidative stress and the impairment of the integrity of the BBB [14,15].…”