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Role of Krüppel-Like Factors in Endothelial Cell Function and Shear Stress–Mediated Vasoprotection
Published in Juhyun Lee, Sharon Gerecht, Hanjoong Jo, Tzung Hsiai, Modern Mechanobiology, 2021
Barrier integrity is another key function of a healthy endothelium regulated by KLF2. The blood–brain barrier is an important structure comprising endothelial cells and controls the trafficking of solutes from the blood into the cerebrospinal fluid. Using a transient ischemic model for stroke via middle cerebral artery occlusion, we found that transgenic KLF2–overexpressing mice were protected from ischemic stroke and had preserved the blood–brain barrier function [114]. Mechanistically this occurs through KLF2-mediated upregulation of the junction protein occludin and phosphorylation of the myosin light chain [103, 114].
Toxic Responses of the Nervous System
Published in Stephen K. Hall, Joana Chakraborty, Randall J. Ruch, Chemical Exposure and Toxic Responses, 2020
As compared to adults, developing fetuses and children are more vulnerable to the effects of certain neurotoxins. This increased vulnerability is attributable to several factors. First, since the nervous system is in an active growing stage in developing fetuses and children, it is often more readily perturbed by certain neurotoxic agents. Secondly, in fetuses and children, the so called “blood-brain barrier” is not yet completely formed. In adults, the blood-brain barrier is composed of a layer of tightly juxtaposed cells in blood vessel walls of the brain which selectively restrict entry of molecules to those necessary for metabolic function. Finally, in fetuses and children, metabolic pathways which detoxify potentially damaging xenobiotics such as neurotoxins are not fully developed. Thus, exposure to neurotoxic agents which the adult may tolerate or overcome may permanently damage the more sensitive nervous system of the developing fetus or child.
Nanoparticles in Cancer Treatment: Types and Preparation Methods
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Jyoti Ahlawat, Emmanuel Zubia, Mahesh Narayan
The delivery of therapeutic drugs to the central nervous system has always presented a special challenge due to the blood–brain barrier. The blood–brain barrier is an endothelial cell lining with tight junctions bounded to a basement membrane and astrocytes. It is hydrophobic in nature and effective at preventing the diffusion of hydrophilic molecules and pathogens from entering the brain parenchyma. One-way nanoparticles could pass this barrier is by coating them with surfactants such as polysorbate, and poly(butyl)cyanoacrylate [8].
Astrocyte 3D culture and bioprinting using peptide functionalized hyaluronan hydrogels
Published in Science and Technology of Advanced Materials, 2023
Isabelle Matthiesen, Michael Jury, Fatemeh Rasti Boroojeni, Saskia L. Ludwig, Muriel Holzreuter, Sebastian Buchmann, Andrea Åman Träger, Robert Selegård, Thomas E. Winkler, Daniel Aili, Anna Herland
Of all the cells that make up the human brain, astrocytes are the most abundant cell type. Astrocytes are involved in synapse formation and function, as well as metabolic activities to support neurons through glutamate clearance at the synaptic cleft [1–3]. Astrocytes also constitute a key role in the formation of the gliovascular unit, where they interact with brain endothelial cells, pericytes, and vascular smooth muscle cells as well as extracellular matrix (ECM) components to form the blood–brain barrier (BBB). The BBB regulates the homeostasis of the central nervous system by controlling transport and exchange of molecules between the blood and the brain [4]. In addition to cell–cell interactions, astrocytes interact extensively with the ECM and the gliovascular basal lamina components of the BBB [5]. The basal lamina is rich in laminins and primarily interacts with the astrocytic endfeet [6]. The interactions between astrocytes and the ECM are also thought to influence the astrocytic response to injury, inflammation, and disease [7].
Green synthesis of nickel nanoparticles using Fumaria officinalis as a novel chemotherapeutic drug for the treatment of ovarian cancer
Published in Journal of Experimental Nanoscience, 2021
Yan Huang, Chunxia Zhu, Rongkai Xie, Ming Ni
Applications of nanoparticles in drug delivery include drug carriers in diseases such as cancer, cardiovascular disease, and Alzheimer's. The use of these nanocarriers is very effective for neurological diseases such as Alzheimer's. Due to their size, these nanoparticles can cross the blood-brain barrier, which has always been a barrier to the passage of drugs to the affected area in this type of destructive brain disease. Due to their small size, nanoparticles can also be used in brain cancers [3]. The goal in making nanoparticles is to control the surface properties, particle size, and release of a specific and efficient drug in a specific place and time for the drug to be as effective as possible. Nanoparticles are widely used in tissue engineering scaffolds, targeted drug delivery, and disease diagnosis. At present, many drug delivery systems are made of nanoparticles and different materials have been used as drug stimulants or enhancers to ameliorate the effectiveness of treatment and the durability and stability as well as the safety of anticancer drugs [1, 2]. The substances used to release cancer drugs are divided into different polymers, magnetic, and biomolecules. These materials can also provide surface modifications such as binding to target antibodies and ligands to make the nanoparticles act purposefully to increase the effectiveness of the treatment [2].
Parecoxib exhibits anti-inflammatory and neuroprotective effects in a rat model of transient global cerebral ischemia
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Shaoxing Liu, Yue’e Dai, Chen Zhou, Tao Zhu
BBB conserves a unique regulatory system to maintain barrier tightness while enabling adequate transport between neurovascular units. The structural and functional integrity of BBB is important to protect the neuronal microenvironment from circulating harmful substances. Cerebral ischemic reperfusion injury initiates a significant inflammatory response, initiating BBB damage and brain edema. IL-1β and TNF-α were found to directly induce endothelial cell injury and BBB disruption (Kempuraj et al. 2016; Mantle and Lee 2018). Immune and inflammatory cells and inflammatory mediators from the periphery traverse the defective BBB and augment neuroinflammation. Blood-brain barrier dysfunction was associated with apoptosis and inflammation, which promotes the development of ischemic brain injury (Lakhan, Kirchgessner, and Hofer 2018). Data demonstrated that tGCI significantly enhanced cerebral vascular leakage as evidenced by EB extravasation and wet weight/dry weight ratio (W/D). Parecoxib significantly decreased the brain water content and EB extravasation at 72 hr after tGCI.