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Overcoming Brain Barriers

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Dear Colleagues,

It is noticeable that the development of therapies for central nervous system (CNS) disorders is a major challenge due to the unique characteristics of complex protective barriers separating the brain from the blood. Restricted drug delivery to the CNS is most frequently attributed to the blood–brain barrier (BBB), which separates the systemic circulation from the CNS; however, additional biological barriers must also be recognized and addressed, particularly the blood–cerebrospinal fluid barrier (BCSFB) which separates the cerebrospinal compartment from the blood circulation. In fact, this security system is responsible for the deficient brain bioavailability of several pharmacological agents to treat CNS diseases. Therefore, effectively and safely delivering therapeutic drugs to the CNS is becoming more important than ever. Thus, focusing on new strategies to overcome brain barriers may offer added-value and a new perspective for the treatment of CNS diseases.

This Special Issue intends to highlight novel findings on the development of new strategies to cross barrier challenges. Improved knowledge on the physiology of brain barriers and of the circumstances that change the drug concentration in the brain is required.

Dr. Telma Quintela
Dr. Cecília R. Santos
Dr. Isabel Goncalves
Guest Editors

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Keywords

choroid plexus
blood–cerebrospinal fluid barrier
blood–brain barrier
brain disorders
drug delivery

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Review

28 pages, 2722 KiB

Open AccessReview

The Role of Biological Rhythms in New Drug Formulations to Cross the Brain Barriers

by Rafael Mineiro, Tânia Albuquerque, Ana Raquel Neves, Cecília R. A. Santos, Diana Costa and Telma Quintela

Int. J. Mol. Sci. 2023, 24(16), 12541; https://doi.org/10.3390/ijms241612541 - 08 Aug 2023

Cited by 1 | Viewed by 1343

Abstract

For brain protection, the blood–brain barrier and blood–cerebrospinal fluid barrier limit the traffic of molecules between blood and brain tissue and between blood and cerebrospinal fluid, respectively. Besides their protective function, brain barriers also limit the passage of therapeutic drugs to the brain, which constitutes a great challenge for the development of therapeutic strategies for brain disorders. This problem has led to the emergence of novel strategies to treat neurological disorders, like the development of nanoformulations to deliver therapeutic agents to the brain. Recently, functional molecular clocks have been identified in the blood–brain barrier and in the blood–cerebrospinal fluid barrier. In fact, circadian rhythms in physiological functions related to drug disposition were also described in brain barriers. This opens the possibility for chronobiological approaches that aim to use time to improve drug efficacy and safety. The conjugation of nanoformulations with chronobiology for neurological disorders is still unexplored. Facing this, here, we reviewed the circadian rhythms in brain barriers, the nanoformulations studied to deliver drugs to the brain, and the nanoformulations with the potential to be conjugated with a chronobiological approach to therapeutic strategies for the brain. Full article

(This article belongs to the Special Issue Overcoming Brain Barriers)

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19 pages, 1127 KiB

Open AccessReview

Transport in the Brain Extracellular Space: Diffusion, but Which Kind?

by Eugene B. Postnikov, Anastasia I. Lavrova and Dmitry E. Postnov

Int. J. Mol. Sci. 2022, 23(20), 12401; https://doi.org/10.3390/ijms232012401 - 17 Oct 2022

Cited by 9 | Viewed by 1659

Abstract

The mechanisms of transport of substances in the brain parenchyma have been a hot topic in scientific discussion in the past decade. This discussion was triggered by the proposed glymphatic hypothesis, which assumes a directed flow of cerebral fluid within the parenchyma, in contrast to the previous notion that diffusion is the main mechanism. However, when discussing the issue of “diffusion or non-diffusion”, much less attention was given to the question that diffusion itself can have a different character. In our opinion, some of the recently published results do not fit into the traditional understanding of diffusion. In this regard, we outline the relevant new theoretical approaches on transport processes in complex random media such as concepts of diffusive diffusivity and time-dependent homogenization, which expands the understanding of the forms of transport of substances based on diffusion. Full article

(This article belongs to the Special Issue Overcoming Brain Barriers)

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