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Hybrid Nanosystems
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Pablo Vicente Torres-Ortega, Laura Saludas, Jon Eneko Idoyaga, Carlos Rodríguez-Nogales, Elisa Garbayo, María José Blanco-Prieto
Treatments aiming to stop the progression of brain-related disorders are often nonspecific and focused on the resolution of short-term symptoms. The delivery of therapeutics across the blood-brain barrier represents another limiting challenge in the treatment of these diseases. Hybrid nanosystems (HNs), defined as the combination of inorganic and organic compounds in a single nanocarrier, offer a new generation of multifunctional nanoparticles (NPs) with superior biological and structural properties. HNs could contribute not only to the design of more effective therapies for brain disorders but also to the development of new theranostic strategies which combine therapeutic and diagnostic functions in a single system.
The patient with acute neurological problems
Published in Peate Ian, Dutton Helen, Acute Nursing Care, 2020
The blood–brain barrier is an important structure that prevents harmful substances in the bloodstream from entering brain tissue. The blood–brain barrier has two main components: a thick capillary basement membrane and tight junctions between the endothelial cells of the capillaries. Capillaries in other parts of the body have gaps between the endothelial cells that allow substances to diffuse across the capillary wall and enter the interstitial space. Tight junctions in brain capillaries and the thick basement membrane prevents diffusion, the brain relies on astrocytes to control the movement of substances from blood to brain. The foot processes of astrocytes press tightly against the endothelial wall of brain capillaries, secreting chemicals that control the permeability of the capillary. This structure is semipermeable to some water-soluble substances like glucose, but not others, for example, proteins and antibiotics. However, it is permeable to fat-soluble substances, e.g., oxygen, carbon dioxide, alcohol and most anaesthetic agents (Tortora and Derrickson 2017). The blood–brain barrier is affected by trauma and inflammation and can malfunction.
Blood–Brain Barrier and Cerebrospinal Fluid (CSF)
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Slow diffusion of many substances between the blood and the cerebrospinal fluid (CSF) suggests the existence of a blood–brain barrier and a blood–CSF barrier (Figure 5.1a and b). The blood–brain barrier is a physiological barrier between the capillaries and the extracellular fluid of the brain that provides a favourable environment for nervous tissue function by selective permeability to substances present in plasma. Morphologically, these barriers are formed by the capillary endothelium and the specialized ependymal cells at the brain–CSF interface. The blood–brain barrier is formed by the capillaries in the brain and prevents the free diffusion of circulating substances into the brain interstitial space. Capillary endothelial cells have the following distinct features: (i) tight junctions (zona occludens) between adjacent cells, (ii) absence of fenestrations and (iii) a high content of mitochondria. Beyond the basement membrane of the capillary endothelium, there is a perivascular area of closely applied foot processes of the astrocytes with intercellular clefts or channels. The blood–CSF barrier is absent in the circumventricular organs, which abut on the third and fourth ventricles. These structures have capillaries that are porous with fenestrations and include the median eminence (hypothalamus), chemoreceptor trigger zone, subfornical organ and pineal gland.
Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients
Published in Annals of Medicine, 2023
Michał Gil, Magdalena Knetki-Wróblewska, Przemysław Niziński, Maciej Strzemski, Paweł Krawczyk
The integrity of the BBB corresponds to 2 types of cells connections. Tight-type junctions are composed of occludins, claudins, and cell adhesion proteins as well as proteins associated with the actin cytoskeleton. Occludins are a 60 kDa phosphoprotein that regulates transmembrane transport by maintaining an appropriate electrical resistance. Claudins are a family of 24 proteins that build tight junctions [6,7,9]. Cell adhesion proteins are immunoglobulins. The cytoplasmic proteins zonula occludens are the most important proteins in this type of junction, they bind occludins, claudins and adhesion proteins to the actin cytoskeleton. The second type of connections are adherence bonds in which the main components are catherins [6–8,10]. The blood-brain barrier has many functions. It allows to maintain the appropriate concentration of ions for the proper functioning of neurons and protects the brain from the excessive activity of neurotransmitters. The BBB performs nutritional functions through numerous transport channels and protects the brain from the action of exo- and endogenous toxins, such as harmful metabolites, drugs or xenobiotics. It also stops most of the proteins from reaching the brain [6,7,10].
Mechanisms of Porphyromonas gingivalis to translocate over the oral mucosa and other tissue barriers
Published in Journal of Oral Microbiology, 2023
Caroline A. de Jongh, Teun J. de Vries, Floris J. Bikker, Susan Gibbs, Bastiaan P. Krom
In the case of being a risk factor for Alzheimer’s disease, in addition to the oral mucosa the bacterium would also need to pass the blood–brain barrier (BBB). Being composed of many cell types, the BBB is another challenging structural and functional barrier for microorganisms. The vessels in the brain do not contain any pores and its cells are tightly adhered together [87]. Transport across the barrier is regulated by specific transport proteins. This makes the blood–brain barrier highly selective and it is specialized to protect the brain against pathogens and toxins [88,89]. However, infection of the brain has been known to occur for various microorganisms. Multiple reviews about bacterial translocation of the BBB describe three of the four mechanisms described in the current review, including: disruption of adherence molecules, transcytosis and the ‘Trojan Horse’ mechanism via macrophages [90–92]. Research into the blood–brain barrier is challenging as it is difficult to represent this barrier in vitro.
Targeting adverse effects of antiseizure medication on offspring: current evidence and new strategies for safety
Published in Expert Review of Neurotherapeutics, 2023
Leihao Sha, Xihao Yong, Zhenhua Shao, Yifei Duan, Qiulei Hong, Jifa Zhang, Yunwu Zhang, Lei Chen
Designing or improving drugs that target changes in the blood-brain barrier can increase drug transport to the blood-brain barrier, thereby reducing drug dosage. Several studies have reported that the teratogenic risk of some ASMs is dose-dependent[47,84]. Therefore, lower drug doses may reduce the risk of antiepileptic treatment during pregnancy. Existing studies have designed or modified drugs from the perspective of blood-brain barrier changes to obtain higher blood-brain barrier transport. Targeting tight junction disruption, several studies have been carried out to design nanoencapsulated drugs to reduce drug size and bypass epithelial cells to enter the blood-brain barrier through paracellular pathways[85,86]. From the perspective of the neuroinflammatory response, targeting the pivotal role of IL-1β in epilepsy, the use of IL-1β monoclonal antibodies to modify drugs can significantly increase the blood-brain barrier transport of drugs[76]. In conclusion, utilizing changes in the blood-brain barrier in patients with epilepsy during pregnancy to increase the transport of drugs to the blood-brain barrier and reduce the dosage of drugs is vital for antiepileptic treatment during pregnancy. It is also a potential direction for future research.