Abstract
The blood-brain barrier (BBB) is a dynamic but solid shield in the cerebral microvascular system. It plays a pivotal role in maintaining central nervous system (CNS) homeostasis by regulating the exchange of materials between the circulation and the brain and protects the neural tissue from neurotoxic components as well as pathogens. Here, we discuss the development of the BBB in physiological conditions and then focus on the role of the BBB in cerebrovascular disease, including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Finally, we summarize recent advancements in the development of therapies targeting the BBB and outline future directions and outstanding questions in the field. We propose that BBB dysfunction not only results from, but is causal in the pathogenesis of neurological disorders; the BBB is more a contributor to the disruption of CNS homeostasis than a victim in neurological disorders.
Highlights
The neurovascular unit (NVU) is a functional complex critical to the stability of the central nervous system (CNS) microenvironment and is composed of endothelial cells (ECs), glial cells, pericytes (PCs), neurons, and the extracellular matrix (ECM)
Acute ischemic stroke (AIS) is primarily caused by transient or permanent reduction in cerebral blood flow (CBF) induced by an embolus or thrombosis blocking regional arteries (Dirnagl et al, 1999); it induces a series of pathological events, including blood-brain barrier (BBB) disruption, vasogenic edema, hemorrhagic transformation (HT), and neuronal injury (Sifat et al, 2017)
Cells affected by this damage induce secondary injury, which is characterized by excitotoxicity and oxidative stress caused by cellular dysfunction and the presence of blood components (Qureshi et al, 2009; Shi et al, 2019)
Summary
The neurovascular unit (NVU) is a functional complex critical to the stability of the CNS microenvironment and is composed of endothelial cells (ECs), glial cells, pericytes (PCs), neurons, and the extracellular matrix (ECM). The blood-brain barrier (BBB) is considered the core structure of the NVU (Saint-Pol et al, 2020). It is established by tightly sealed ECs located at the luminal surface of the brain’s vascular tree (Sweeney et al, 2019b). Blood-brain barrier dysfunction is a pathophysiological hallmark in the pathogenesis of multiple CNS diseases (Cummins, 2011). Extensive evidence implicates it in cerebrovascular, neurodegenerative, and neuroinflammatory diseases. We first illustrate the physiological structure of the BBB and discuss the development of junctional complex perturbations in pathological conditions, including cerebrovascular disease and neurodegenerative disorders. We emphasize the significance of the BBB in neurological disorders and put forward crucial questions to be answered in the future
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