scholarly journals Hypoxic-Ischaemic Encephalopathy and the Blood-Brain Barrier in Neonates

2017 ◽  
Vol 39 (1-4) ◽  
pp. 49-58 ◽  
Author(s):  
Wei Ling Amelia Lee ◽  
Adina T. Michael-Titus ◽  
Divyen K. Shah
Keyword(s):  
Blood Brain Barrier ◽  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Cerebral Injury ◽  
Brain Barrier ◽  
Transport Systems ◽  
Permeability Barrier ◽  
Cell Based Therapy ◽  
Blood Brain ◽  
The Brain

This review aims to highlight a possible relationship between hypoxic-ischaemic encephalopathy (HIE) and the disruption of the blood-brain barrier (BBB). Inflammatory reactions perpetuate a large proportion of cerebral injury. The extent of injury noted in HIE is not only determined by the biochemical cascades that trigger the apoptosis-necrosis continuum of cell death in the brain parenchyma, but also by the breaching of the BBB by pro-inflammatory factors. We examine the changes that contribute to the breakdown of the BBB that occur during HIE at a macroscopic, cellular, and molecular level. The BBB is a permeability barrier which separates a large majority of brain areas from the systemic circulation. The concept of a physiological BBB is based at the anatomical level on the neurovascular unit (NVU). The NVU consists of various cellular components that jointly regulate the exchanges that occur at the interface between the systemic circulation and the brain parenchyma. There is increased understanding of the contribution of the components of the NVU, e.g., astrocytes and pericytes, to the maintenance of this physiological barrier. We also explore the development of therapeutic options in HIE, such as harnessing the transport systems in the BBB, to enable the delivery of large molecules with molecular Trojan horse technology, and the reinforcement of the physical barrier with cell-based therapy which utilizes endothelial progenitor cells and stem cells.

scholarly journals The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1833
Author(s):  
Shannon Morgan McCabe ◽  
Ningning Zhao
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Blood Circulation ◽  
Critical Role ◽  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.

IMMUNOHISTOCHEMICAL STUDIES OF BLOOD BRAIN BARRIER AFTER ADMINISTRATION OF ABHRAK BHASM IN WISTAR RATS

2021 ◽  
pp. 13-19
Author(s):  
Amita Singh ◽  
Raj Kumar ◽  
S. K. Kannaujia ◽  
Manikrishna Manikrishna ◽  
N. P. Singh
Keyword(s):  
Blood Brain Barrier ◽  
Wistar Rats ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Major Constituent ◽  
Control Group ◽  
Blood Brain ◽  
Biological Studies ◽  
Immunohistochemical Studies ◽  
The Brain

Abhrak bhasma (AB) is a type of bhasma prepared from repeated incineration of mineral mica with decoctions of about 72 herbs. The particle size of Abhrak bhasm has been shown to be in the range of 29-88 nanometers and Fe, Ca, Si, Mg and K are found to be as major constituent. Many drugs developed to treat Central Nervous System (CNS) disorders are unable to reach the brain parenchyma in therapeutically relevant concentrations. The blood brain barrier protects brain parenchyma from the uctuation of plasma composition, from pathogenic agents and maintains homeostasis of the brain parenchyma by restricting non-specic ux of ions, peptides, proteins and even cells into and out the brain. Immunohistochemistry is being widely employed as a tool for biological studies. This study is conducted to examine the change in the continuity of Blood brain barrier by using immunohistochemistry, once Abhrak bhasm drug is given in experimental animal and also to examine the histology of organs. In this study a total of 30 adult albino Wistar rats of approximately 4 months age (approx. 150-200 gms) of either sex selected randomly to see the effect of Abhrak bhasm, an ayurvedic drug on Wistar rats. The rats were weighed, marked and divided into 5 groups each consisting of six animals. In normal control group (Group E), no drug was administered and in rest of the four treated groups (Group-A,B,C,D), Abhrak bhasm @ 36 mg/kg B.wt. was administered orally once in each rat. Brain, liver, kidneys,spleen and blood samples were collected in 10% formalin solution after euthanizing the rats at 0.5,2,6 & 12 hours of Abhrak bhasma drug intervention. The alterations in any of the biochemical parameters are within the tolerable limits of liver and kidney since the dose of abhrak bhasm did not affect liver and kidneys. In the present study, the increase in ALP level may be the result of alterations in metabolisms that occurred without any signicant alteration in histology of liver. After applying the immunohistochemistry with the research markers GFAP, CD 34, S 100, GLUT-1 and RECA-1 on the rats in groups A,B,C and D, there was no change in the intensity of immunohistochemistry, with respect to control. While on applying the Occludin, the intensity of immunohistochemistry was reduced in all the treatment groups as compared to the control group. On the basis of ndings of present study it can be concluded that the therapeutic dose of Abhrak bhasma causes changes at the level of tight junctions present in blood brain barrier in rats which is shown by immunohistochemistry with occludin research marker. There is no toxic effect of drug on different organs of rats as no signicant changes in histology of organs are seen. More studies need to be done to check the permeability of blood brain barrier for Abhrak bhasma drug, like calculating its concentration in brain tissues and other vital organs of rat.

scholarly journals In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use

2016 ◽  
Vol 36 (5) ◽  
pp. 862-890 ◽  
Author(s):  
Hans C Helms ◽  
N Joan Abbott ◽  
Malgorzata Burek ◽  
Romeo Cecchelli ◽  
Pierre-Olivier Couraud ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
Culture Models ◽  
Cell Culture Models ◽  
The Brain

The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This “blood-brain barrier” function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood–brain barrier models with a focus on their validation regarding a set of well-established blood–brain barrier characteristics. As an ideal cell culture model of the blood–brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described.

scholarly journals Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides.

1995 ◽  
Vol 182 (4) ◽  
pp. 1037-1043 ◽  
Author(s):  
B Spellerberg ◽  
S Prasad ◽  
C Cabellos ◽  
M Burroughs ◽  
P Cahill ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Dependent Manner ◽  
Pharmacological Agents ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain

The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis. By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents < or = 20 kD in size. Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the brain parenchyma.

scholarly journals Structural, Molecular, and Functional Alterations of the Blood-Brain Barrier during Epileptogenesis and Epilepsy: A Cause, Consequence, or Both?

2020 ◽  
Vol 21 (2) ◽  
pp. 591 ◽  
Author(s):  
Wolfgang Löscher ◽  
Alon Friedman
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Defense Mechanism ◽  
Extracellular Fluid ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Brain Barrier ◽  
Transport Systems ◽  
Blood Brain ◽  
The Brain

The blood-brain barrier (BBB) is a dynamic, highly selective barrier primarily formed by endothelial cells connected by tight junctions that separate the circulating blood from the brain extracellular fluid. The endothelial cells lining the brain microvessels are under the inductive influence of neighboring cell types, including astrocytes and pericytes. In addition to the anatomical characteristics of the BBB, various specific transport systems, enzymes and receptors regulate molecular and cellular traffic across the BBB. While the intact BBB prevents many macromolecules and immune cells from entering the brain, following epileptogenic brain insults the BBB changes its properties. Among BBB alterations, albumin extravasation and diapedesis of leucocytes from blood into brain parenchyma occur, inducing or contributing to epileptogenesis. Furthermore, seizures themselves may modulate BBB functions, permitting albumin extravasation, leading to activation of astrocytes and the innate immune system, and eventually modifications of neuronal networks. BBB alterations following seizures are not necessarily associated with enhanced drug penetration into the brain. Increased expression of multidrug efflux transporters such as P-glycoprotein likely act as a ‘second line defense’ mechanism to protect the brain from toxins. A better understanding of the complex alterations in BBB structure and function following seizures and in epilepsy may lead to novel therapeutic interventions allowing the prevention and treatment of epilepsy as well as other detrimental neuro-psychiatric sequelae of brain injury.

scholarly journals Disturbance of Intracerebral Fluid Clearance and Blood–Brain Barrier in Vascular Cognitive Impairment

2019 ◽  
Vol 20 (10) ◽  
pp. 2600 ◽  
Author(s):  
Masaki Ueno ◽  
Yoichi Chiba ◽  
Ryuta Murakami ◽  
Koichi Matsumoto ◽  
Ryuji Fujihara ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Brain Function ◽  
Vascular Cognitive Impairment ◽  
Brain Dysfunction ◽  
Brain Parenchyma ◽  
The Other ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

The entry of blood-borne macromolecular substances into the brain parenchyma from cerebral vessels is blocked by the blood–brain barrier (BBB) function. Accordingly, increased permeability of the vessels induced by insult noted in patients suffering from vascular dementia likely contributes to the cognitive impairment. On the other hand, blood-borne substances can enter extracellular spaces of the brain via endothelial cells at specific sites without the BBB, and can move to brain parenchyma, such as the hippocampus and periventricular areas, adjacent to specific sites, indicating the contribution of increased permeability of vessels in the specific sites to brain function. It is necessary to consider influx and efflux of interstitial fluid (ISF) and cerebrospinal fluid (CSF) in considering effects of brain transfer of intravascular substances on brain function. Two pathways of ISF and CSF are recently being established. One is the intramural peri-arterial drainage (IPAD) pathway of ISF. The other is the glymphatic system of CSF. Dysfunction of the two pathways could also contribute to brain dysfunction. We review the effects of several kinds of insult on vascular permeability and the failure of fluid clearance on the brain function.

Metabolic fuel and amino acid transport into the brain in experimental hypothyroidism

1990 ◽  
Vol 122 (2) ◽  
pp. 156-162 ◽  
Author(s):  
Arshag D. Mooradian
Keyword(s):  
Amino Acids ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transport Systems ◽  
Brain Uptake ◽  
Acid Transport ◽  
Brain Extraction ◽  
Blood Brain ◽  
Brain Uptake Index ◽  
The Brain

Abstract The effect of hypothyroidism in the adult rat on blood-brain barrier and muscle transport of hexoses, neutral amino acids, basic amino acids, monocarboxylic acids, and ketone bodies was examined using single arterial injection-tissue sampling technique. The cerebral blood flow and brain extraction of 3H2O (internal reference substance) was not altered in 3-month-old hypothyroid rats maintained on methimazole, 0.025% in the drinking water, for 7 weeks. The brain uptake index of D-β-hydroxybutyrate was significantly reduced in hypothyroid rats (2.4 ± 0.3 vs 4.6 ± 0.6% p<0.001). Hypothyroid rats given thyroid hormone replacement therapy had normal brain uptake of D-β-hydroxybutyrate (4.4 ± 0.8%). The brain uptake index of butyrate was also significantly reduced in hypothyroid rats (39.3 ± 2.1 vs 47.2 ± 0.74%, p<0.001). The brain uptake index of other test substances and muscle uptake of nutrients examined were not altered in hypothyroid rats. These studies indicate that of the four transport systems examined in two tissues, the blood-brain barrier monocarboxylic acid transport system is most susceptible to the hypothyroidism-induced changes.

scholarly journals Heparin-derived theranostic nanoprobes overcome the blood-brain barrier and target glioma in murine model

2022 ◽  
Author(s):  
Sumanta Samanta ◽  
Vadim Le Joncour ◽  
Olivia Wegrzyniak ◽  
Vigneshkumar Rangasami ◽  
Harri Ali-Loytty ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Xenograft Model ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Treatment Modalities ◽  
Mouse Strains ◽  
Tail Vein ◽  
Blood Brain ◽  
Theranostic Agents ◽  
The Brain

The poor permeability of theranostic agents across the blood-brain-barrier (BBB) significantly hampers the development of new treatment modalities for neurological diseases. We have discovered a new biomimetic nanocarrier using heparin (HP) that effectively passes the BBB and targets glioblastoma. Specifically, we designed HP coated gold nanoparticles (HP-AuNPs) that were labeled with three different imaging modalities namely, fluorescein (FITC-HP-AuNP), radioisotope 68Gallium (68Ga-HP-AuNPs), and MRI active gadolinium (Gd-HP-AuNPs). The systemic infusion of FITC-HP-AuNPs in three different mouse strains (C57BL/6JRj, FVB, and NMRI-nude) displayed excellent penetration and revealed uniform distribution of fluorescent particles in the brain parenchyma (69-86%) with some accumulation in neurons (8-18%) and microglia (4-10%). Tail-vein administration of radiolabeled 68Ga-HP-AuNPs in healthy rats also showed 68Ga-HP-AuNP inside the brain parenchyma and in areas containing cerebrospinal fluid, such as the lateral ventricles, the cerebellum, and brain stem. Finally, tail-vein administration of Gd-HP-AuNPs (that display ~3 fold higher relaxivity than that of commercial Gd-DTPA) in an orthotopic glioblastoma (U87MG xenograft) model in nude mice demonstrated enrichment of T1-contrast at the intracranial tumor with a gradual increase in the contrast in the tumor region between 1h-3h. We believe, our finding offers the untapped potential of HP-derived-NPs to deliver cargo molecules for treating neurological disorders.

scholarly journals A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

Membranes ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 212 ◽  
Author(s):  
Hernán Cortés ◽  
Sergio Alcalá-Alcalá ◽  
Isaac H. Caballero-Florán ◽  
Sergio A. Bernal-Chávez ◽  
Arturo Ávalos-Fuentes ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Transport Systems ◽  
Future Directions ◽  
Blood Brain ◽  
Dynamic Interface ◽  
And Function ◽  
The Brain

The blood-brain barrier (BBB) is a sophisticated and very selective dynamic interface composed of endothelial cells expressing enzymes, transport systems, and receptors that regulate the passage of nutrients, ions, oxygen, and other essential molecules to the brain, regulating its homeostasis. Moreover, the BBB performs a vital function in protecting the brain from pathogens and other dangerous agents in the blood circulation. Despite its crucial role, this barrier represents a difficult obstacle for the treatment of brain diseases because many therapeutic agents cannot cross it. Thus, different strategies based on nanoparticles have been explored in recent years. Concerning this, chitosan-decorated nanoparticles have demonstrated enormous potential for drug delivery across the BBB and treatment of Alzheimer’s disease, Parkinson’s disease, gliomas, cerebral ischemia, and schizophrenia. Our main objective was to highlight the high potential of chitosan adsorption to improve the penetrability through the BBB of nanoformulations for diseases of CNS. Therefore, we describe the BBB structure and function, as well as the routes of chitosan for crossing it. Moreover, we define the methods of decoration of nanoparticles with chitosan and provide numerous examples of their potential utilization in a variety of brain diseases. Lastly, we discuss future directions, mentioning the need for extensive characterization of proposed nanoformulations and clinical trials for evaluation of their efficacy.

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