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 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.

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 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.

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 Protection Against Blood-brain Barrier Permeability as a Possible Mechanism for Protective Effects of Thymoquinone Against Sickness Behaviors Induced by Lipopolysaccharide in Rats

2021 ◽  
Vol 16 (2) ◽  
Author(s):  
Rahimeh Bargi ◽  
Mahmoud Hosseini ◽  
Fereshteh Asgharzadeh ◽  
Majid Khazaei ◽  
Mohammad Naser Shafei ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Active Role ◽  
Brain Barrier ◽  
Control Group ◽  
Protective Effects ◽  
Blood Brain ◽  
Immobility Time ◽  
Sickness Behaviors ◽  
Bbb Permeability ◽  
The Brain

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

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 Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Kasper Bendix Johnsen ◽  
Annette Burkhart ◽  
Fredrik Melander ◽  
Paul Joseph Kempen ◽  
Jonas Bruun Vejlebo ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Transferrin Receptors ◽  
Cargo Transport ◽  
Blood Brain ◽  
The Brain

scholarly journals Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Blake H. Albright ◽  
Katherine E. Simon ◽  
Minakshi Pillai ◽  
Garth W. Devlin ◽  
Aravind Asokan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sialic Acid ◽  
Blood Brain Barrier ◽  
Viral Vectors ◽  
Variable Region ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

ABSTRACT Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB). We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown. Here, we establish through structural modeling that this footprint overlaps in part the sialic acid (SIA) footprint on AAV1. We hypothesized that altered SIA-capsid interactions may influence the ability of AAV1RX to transduce the CNS. Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence. Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency. In contrast, AAV1 shows strong SIA dependency and does not transduce the CNS after systemic administration and, instead, transduces the vasculature and the liver. The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10. In corollary, the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1) attenuated CNS transduction relative to that of AAVrh.10. We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype. Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids. IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy. In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.

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