Blood–brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders

Abstract

The integrity of the blood–brain barrier (BBB) is essential for normal central nervous system (CNS) functioning. Considering the significance of BBB in maintaining homeostasis and the neural environment, we aim to provide an overview of significant aspects of BBB. Worldwide, the treatment of neurological diseases caused by BBB disruption has been a major challenge. BBB also restricts entry of neuro-therapeutic drugs and hinders treatment modalities. Hence, currently nanotechnology-based approaches are being explored on large scale as alternatives to conventional methodologies. It is necessary to investigate the in-depth characteristic features of BBB to facilitate the discovery of novel drugs that can successfully cross the barrier and target the disease effectively. It is imperative to discover novel strategies to treat life-threatening CNS diseases in humans. Therefore, insights regarding building blocks of BBB, activation of immune response on breach of this barrier, and various autoimmune neurological disorders caused due to BBB dysfunction are discussed. Further, special emphasis is given on delineating BBB disruption leading to CNS disorders. Moreover, various mechanisms of transport pathways across BBB, several novel strategies, and alternative routes by which drugs can be properly delivered into CNS are also discussed.

Need for a Paradigm Shift in the Treatment of Ischemic Stroke: The Blood-Brain Barrier

“…All this cellular functional group constitutes the neurovascular unit ( Figure 2 a). Therefore, the normal functioning of the BBB requires an adequate interaction between a luminal component, consisting of specific endothelial cells reinforced by pericytes and a vascular basement membrane, and an abluminal component consisting of an extracellular matrix, astrocytes, microglia, macrophages, and neurons [ 34 , 35 , 36 , 37 ].…”

Key brain cell interactions and contributions to the pathogenesis of Alzheimer’s disease

“…In contrast with ECs from other tissues, BBB ECs present particular features that allow them to effectively control the transport of ions, molecules, and cells between the blood and the brain ( Daneman and Prat, 2015 ; Alajangi et al, 2022 ). Intercellular junctions between ECs play a critical role in vascular integrity and permeability barrier function ( Vestweber, 2012 ).…”

“…This strong paracellular and transcellular barrier forms a polarized cell with distinct luminal and abluminal membrane compartments, allowing tight regulation of movement between the blood and the brain via regulated cellular transport features ( Chow and Gu, 2015 ). The transporters expressed by CNS ECs fall into two types: efflux transporters and specific nutrient transporters ( Alajangi et al, 2022 ). Efflux transporters transport a large variety of lipophilic molecules into the blood, while nutrient transporters guarantee the provision of particular nutrients across the BBB and help in waste elimination by transporting waste products from the CNS into the blood ( Mittapalli et al, 2010 ).…”

“…Efflux transporters transport a large variety of lipophilic molecules into the blood, while nutrient transporters guarantee the provision of particular nutrients across the BBB and help in waste elimination by transporting waste products from the CNS into the blood ( Mittapalli et al, 2010 ). For the delivery of nutrients into the CNS parenchyma, CNS ECs express slc2a1GLUT1 for glucose transport, slc7a1 for cationic amino acid transport, slc16a1 and L-DOPA for lactate and pyruvate supply, and slc7a5 for neutral amino acid transport ( Daneman and Prat, 2015 ; Alajangi et al, 2022 ). Several studies suggest that, at the BBB, ECs seem to rely on glycolysis to generate ATP ( Kim et al, 2022 ), and to use mitochondrial respiration as secondary source of energy production.…”

Advances in the study of the relationship between Alzheimer's disease and the gastrointestinal microbiome

“…Precisely, its deficit resulted in a reduction in connexin in the TJ, directly affecting BBB permeability and significantly increasing the risk of brain injury 31–33 . Although it is not clear why GLUT1 expression is reduced in AD patients, it is apparent that its reduction not only leads to an insufficient supply of nutrients in the brain but also to BBB disintegration when this reduction occurs in the endothelium 33,34 …”