Oxidative Stress-Mediated Blood-Brain Barrier (BBB) Disruption in Neurological Diseases

The blood-brain barrier (BBB), as a crucial gate of brain-blood molecular exchange, is involved in the pathogenesis of multiple neurological diseases. Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the scavenger system. Since oxidative stress plays a significant role in the production and maintenance of the BBB, the cerebrovascular system is especially vulnerable to it. The pathways that initiate BBB dysfunction include, but are not limited to, mitochondrial dysfunction, excitotoxicity, iron metabolism, cytokines, pyroptosis, and necroptosis, all converging on the generation of ROS. Interestingly, ROS also provide common triggers that directly regulate BBB damage, parameters including tight junction (TJ) modifications, transporters, matrix metalloproteinase (MMP) activation, inflammatory responses, and autophagy. We will discuss the role of oxidative stress-mediated BBB disruption in neurological diseases, such as hemorrhagic stroke, ischemic stroke (IS), Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and cerebral small vessel disease (CSVD). This review will also discuss the latest clinical evidence of potential biomarkers and antioxidant drugs towards oxidative stress in neurological diseases. A deeper understanding of how oxidative stress damages BBB may open up more therapeutic options for the treatment of neurological diseases.