Stroke-induced damage on the blood–brain barrier

Abstract

The blood–brain barrier (BBB) is a functional phenotype exhibited by the neurovascular unit (NVU). It is maintained and regulated by the interaction between cellular and non-cellular matrix components of the NVU. The BBB plays a vital role in maintaining the dynamic stability of the intracerebral microenvironment as a barrier layer at the critical interface between the blood and neural tissues. The large contact area (approximately 20 m2/1.3 kg brain) and short diffusion distance between neurons and capillaries allow endothelial cells to dominate the regulatory role. The NVU is a structural component of the BBB. Individual cells and components of the NVU work together to maintain BBB stability. One of the hallmarks of acute ischemic stroke is the disruption of the BBB, including impaired function of the tight junction and other molecules, as well as increased BBB permeability, leading to brain edema and a range of clinical symptoms. This review summarizes the cellular composition of the BBB and describes the protein composition of the barrier functional junction complex and the mechanisms regulating acute ischemic stroke-induced BBB disruption.

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“…The BBB is a dynamic barrier composed of brain microvessel endothelial cells (ECs), pericytes, astrocytes, and a basement membrane, which regulates the exchange of molecules between the bloodstream and the brain. Each component plays a crucial role in maintaining the barrier’s integrity and selective permeability [ 33 , 34 , 35 , 36 , 37 ]: ECs feature specialised transport systems for selective transcytosis, and tight junctions limit paracellular transport [ 64 ]. Pericytes contribute to BBB maturation and stabilisation, possessing contractile properties that influence blood flow [ 64 ].…”

“…They release factors such as NO and VEGF, impacting vasodilation and oedema. Astrocyte–endothelial cell interactions induce specific phenotypes crucial for maintaining BBB homeostasis, especially during neuroinflammation following IS [ 37 , 65 ].…”

“…The endothelial glycocalyx layer and the expression of leukocyte adhesion molecules further modulate the BBB permeability. Equipped with a comprehensive molecular transport system, the BBB maintains brain homeostasis by facilitating essential nutrient transport and preventing toxic compound accumulation [ 37 , 65 ].…”

“…For instance, pericyte loss has been linked to increased endothelial transcytosis without affecting tight junctions. Understanding these mechanisms is essential for developing interventions targeting BBB dysfunction and improving stroke patient outcomes [ 37 ].…”

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“…In recent years, the incidence rate of brain diseases such as Alzheimer’s disease, Parkinson’s disease, stroke, and brain tumors has continued to increase, which has been hugely detrimental to human health ( Palmer, 2010 ). These changes have led to increased research activity to develop better therapeutic strategies; however, there are many obstacles affecting the development of new drugs for the treatment of such diseases, one of which is the existence of the blood–brain barrier (BBB) ( Palmer, 2010 ; Xue et al, 2023 ). The BBB is a complex multicellular structure with extremely low permeability, which limits the movement of molecules between the blood and the neural tissues comprising the central nervous system (CNS) to help maintain homeostasis ( Xue et al, 2023 ).…”