Blood–brain barrier

Summary

The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function. The blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and large or hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of hydrophobic molecules (O2, CO2, hormones) and small non-polar molecules. Cells of the barrier actively transpor

Official source

https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier

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Recent Developments on the Use of Nanomaterials for the Treatment of Epilepsy

Sara María Garcia Pedrero, Sandrine Gerber

Epilepsy affects more than 40 million people worldwide, constituting one of the most debilitating disorders of the Central Nervous System (CNS). It results from an imbalance in the electrical activity of neurons, which is primarily mediated by calcium ions. In many cases, treatment with Antiepileptic Drugs (AEDs) that regulate calcium channel activity results in successful seizure control. However, AEDs frequently cause adverse effects that range in severity from minimal impairment of the CNS to death from aplastic anemia or hepatic failure. Moreover, 30% of epileptic patients show drug-resistant epilepsy and do not respond to any form of medical treatment. In this context, nanotechnology has emerged as an excellent tool to overcome AEDs limitations. Numerous nano-strategies have been proposed as therapeutics and diagnostics for epilepsy through inhibition of different calcium channel types in the brain. In addition, limited brain access of classical AEDs in patients showing refractory epilepsy could be improved through the design of targeted drug delivery nanosystems. This report presents a review of the nanocarriers developed so far that could facilitate the interaction with calcium channels in the brain and the transport of AEDs through the blood-brain-barrier, mapping out a potential future direction in the research of epilepsy treatment.

2022

The future of medicine lies in therapeutic approaches that can specifically target sites of disease and induce a localized and effective therapeutic effect. Cell-mediated delivery, especially using cells of the circulatory repertoire such as T lymphocytes, represents an extremely attractive opportunity to transport and deliver therapeutic materials across endothelial barriers to sites of inflammation. The work presented in this Thesis explores the feasibility of using a T cell carrier to transport model nanoparticles to the central nervous system (CNS). The use of non-phagocytic cells as carriers, such as T lymphocytes, for the transport of nanomaterials essentially relies on the attachment of the therapeutic cargo on their surface. Cell-surface modification is an emerging field of research with many opportunities for therapy. This work has also tried to address a more fundamental question encountered in this field and describes a novel methodology to precisely and quantitatively determine the localization of nanomaterials on the cell carrier after surface-conjugation. Chapter 1 presents a review of the literature that covers the different approaches used for the attachment of synthetic nano- and microparticles to a variety of cells, spanning from erythrocytes, monocytes and macrophages to T lymphocytes and adult stem cells. This Chapter highlights the (bio)chemical tools that are available to modify cell surfaces with synthetic materials. These methods have been used for the attachment of a variety of synthetic materials such as polymer micron-size patches, polymer nano- and microparticles as well as lipid-based nanomaterials. An emphasis was given to therapeutic applications of the surface modified cells, which can be used to enhance systemic circulation time of nanoparticles or to mediate the transport of nanomaterials to a site of disease or in combination with cell therapy. Chapter 2 explores the use of a cell carrier to mediate the transport of nanoparticles to the CNS. Here CD4+ TEM cells were used as vehicles to deliver polymer nanoparticles across the blood-brain barrier (BBB). In fact, effective delivery of CNS active compounds across the BBB remains as one of the biggest challenges in drug delivery. Polymer model nanoparticles were attached on the surface of T cells using a maleimide-thiol covalent ligation. Nanoparticle decorated T cells were subjected to a series of functional assays to determine the influence of surface-conjugation. In particular, their ability to cross the BBB was assessed and it was demonstrated that surface-modified T cells remained functional and that they were able to transport partially their nanoparticle cargo across the BBB in vitro. The multistep extravasation of nanoparticle modified T cells across the BBB was observed for the first time by means of time-lapse live cell imaging techniques. Chapter 3 capitalizes on a method that was developed in Chapter 2 for the determination of the localization and distribution of nanoparticles on T lymphocytes after surface-conjugation. 3D-reconstruction of confocal micrograph z-stacks followed by image processing provided the distance of fluorescently labelled nanoparticles from the cell surface as function of time. The method developed previously was here challenged with a range of different nanoparticles sizes and across two different cell lines and was validated for semi-quantitative estimation of surface-conjugated versus internalized nanoparticles.

EPFL2017

Phytoextraction of zinc, zinc oxide, copper and copper oxide in hydroponic solution with gibberellic acid and EDDS amendments by Lolium perenne

Flore Alice Margot Dupuich

This work was focused on the phytoextraction of zinc, copper, zinc oxide and copper oxide by Lolium perenne cultivated in hydroponic conditions, with gibberellic acid (GA) and ethylenediamine-N,N’-disuccinic acid (EDDS) amendments tested separately and in combination. GA is a plant hormone which permits a better uptake of trace elements by increasing the biomass of shoots and the transpiration. EDDS is a chelator permitting to the metal to complex and cross physiological barriers. These two amendments were tested separately and in combination because a good synergy effect should be observed. The duration of treatment was first 11 days and then 28 days. The enzyme activity of catalase and ascorbate peroxidase was measured. The results showed a higher uptake for zinc with the GA treatment, where the final quantity after 21 days was 24 μg instead of 14 μg for the control, and the translocation index was 0.3 instead of 0.1 for the control. For copper the best results were obtained with EDDS, which gave a quantity of 4.5 μg after 28 days instead of 3.5 μg for the control and the translocation index was 0.275 instead of 0.12 for the control. For the metal oxides the results were less significant, especially for enzyme activities. Finally a hydric stress was observed after 28 days, cumulated with metal stress.

2013

EPFL2017