Impact of Various Diseases on Brain Barrier Function and Central Nervous System Drug Delivery

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About this Research Topic

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Background

The blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) create a formidable barrier between the Central Nervous System (CNS) and periphery, ensuring the homeostasis of the brain is tightly regulated. This is accomplished by both physical (i.e., tight junctions) and biochemical (i.e., transporters) barrier properties. While these barriers provide effective protection of the brain under healthy conditions, there is a growing body of evidence demonstrating that the status of the BBB and BCSFB is perturbed in both diseases of the CNS and diseases of the periphery. Such disease-induced alterations, including modified expression and function of drug influx and efflux transporters and tight junctions, have the potential to not only impact on CNS homeostasis and brain function, but to also impact CNS exposure of therapeutic agents and cause critical changes to the pharmacokinetic, pharmacodynamic, and toxicokinetic properties of peripherally-administered medicines.

In this Research Topic, we seek to highlight the most recent and state-of-the-art research on the regulation, structure, and function of the BBB and BCSFB in diseases of the CNS and of the periphery. A particular focus on expression and function of influx and efflux transporters and tight junction proteins at the brain barriers will be prioritized, given that these provide the biochemical and physical barriers to CNS access, respectively. The impact of these changes on the progression of these diseases will be evaluated given that altered brain barrier function will lead to potential disturbances in brain homeostasis and therefore, neuronal, astrocytic and microglial function. Furthermore, the impact of these disease-mediated changes on the CNS access of medicines, and their subsequent activity, efficacy and toxicity will be highlighted, providing insight into whether individuals with different diseases are at a higher (or lower) risk of toxicity and efficacy.

This Research Topic welcomes contributions from preclinical and clinical researchers focusing on the status of the BBB and BCSFB in various disease states. These include diseases of the brain such as neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis, neurological diseases like epilepsy and migraine headache, cerebrovascular disorders, traumatic brain injury and peripheral diseases such as diabetes, hyperlipidemia, hepatic diseases, acute/chronic pain and brain infections i.e., HIV, COVID-19. Submissions are welcome for the following article types: original re-search, review, mini-reviews, research protocol/method, opinion and hypothesis.

Keywords: Blood-Brain Barrier, Blood-CSF Barrier, Drug Transporters, CNS Drug Delivery, Tight Junction Protein Complexes, Pathophysiology, CNS Disorders, Nanoformulations for Brain Delivery, Brain Transport Pathways

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