scholarly journals The Role and Mechanism of Borneol to Open the Blood-Brain Barrier

2018 ◽  
Vol 17 (3) ◽  
pp. 806-812 ◽  
Author(s):  
Tao Wu ◽  
Aiqin Zhang ◽  
Hongyang Lu ◽  
Qiaoyuan Cheng
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Corn Oil ◽  
Malignant Tumors ◽  
Brain Barrier ◽  
Control Group ◽  
High Dose ◽  
Total Density ◽  
Sd Rats ◽  
Blood Brain

Background: The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors. Objective: The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms. Materials and Methods: Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected. Thirty minutes later, brain tissue was analyzed using the Evans blue standard curve. Another 40 SD rats were randomized into high-, medium-, and low-dose borneol groups and a control group. Each rat in the experimental groups was intragastrically administered with 10% borneol corn oil (2 mL/kg, 1.25 mL/kg, and 0.5 mL/kg, respectively). The control group was injected with corn oil of 1.25 mL/kg. After 30 minutes, the rats were killed, and the brain tissues were collected. The expression of occludin, occludens-1, nitric oxide synthase, P-glycoprotein, and intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemy. Results: The concentration of Evans blue in the borneol group was higher than in the control group ( P < .05). The mean density of ICAM-1 expression was higher in the experimental group than in the control group ( P < .05). In contrast, significant differences of positive area and total density of ICAM-1 were shown only between the high-dose group and the control group ( P < .05). Conclusion: Borneol can open the BBB, which might be related with the increased expression of ICAM-1.

The influence of nimodipine on cerebral blood flow autoregulation and blood-brain barrier

1988 ◽  
Vol 69 (6) ◽  
pp. 919-922 ◽  
Author(s):  
Hans-Georg Höllerhage ◽  
Michael R. Gaab ◽  
Matthias Zumkeller ◽  
Gerhard F. Walter
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Brain Barrier ◽  
Evans Blue ◽  
Brain Barrier ◽  
Control Group ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Blood Brain ◽  
Anesthetized Rats

✓ Twenty anesthetized rats were randomly assigned to a nimodipine-treated group or a control group of 10 rats each. Local cerebral blood flow (lCBF) was measured by means of a surface electrode using the hydrogen clearance technique. Systemic arterial pressure (SAP) was varied with administration of norfenefrine or by hemorrhage in order to obtain SAP/cerebral blood flow (CBF) curves under different conditions. In the control group, a typical autoregulation curve was obtained with an lCBF plateau between 70 and 120 mm Hg SAP. The nimodipine-treated animals, however, showed only a slight diminution in the slope of the curve but no real plateau, indicating impairment of CBF autoregulation. In another series, 20 anesthetized rats were randomly assigned to a treatment group or a control group of 10 animals each. Intravenous Evans blue dye was used as a tracer for blood-brain barrier (BBB) function. In both groups, SAP was raised to a level of 180 mm Hg with administration of norfenefrine for 6 minutes. Extravasation of significantly more Evans blue dye was observed in the nimodipine group than in the control group, indicating impairment of the BBB. It is concluded that nimodipine may impair CBF autoregulation, allowing damage to the BBB under hypertensive conditions.

Entry of [3H]norepinephrine, [125I]albumin and evans blue from blood into brain following unilateral osmotic opening of the blood-brain barrier

1978 ◽  
Vol 145 (2) ◽  
pp. 291-301 ◽  
Author(s):  
C.C. Chiueh ◽  
C.L. Sun ◽  
I.J. Kopin ◽  
W.R. Fredericks ◽  
S.I. Rapoport
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Brain Barrier ◽  
Blood Brain

Enhanced blood-brain barrier leakage to evans blue-labelled albumin after air embolism in ethanol-intoxicated rats

1977 ◽  
Vol 38 (2) ◽  
pp. 149-152 ◽  
Author(s):  
Lars Rosengren ◽  
Lennart Persson ◽  
Barbro Johansson
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Air Embolism ◽  
Brain Barrier ◽  
Blood Brain

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.

EXTH-07. TEMPORAL ASSESSMENT OF ALTERED PERI-ABLATION BLOOD-BRAIN BARRIER PERMEABILITY FOLLOWING TUMOR CYTOREDUCTION BY THERMAL THERAPY IN A RAT ORTHOTOPIC GLIOBLASTOMA MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi164-vi164
Author(s):  
Tavarekere Nagaraja ◽  
Seamus Bartlett ◽  
Glauber Cabral ◽  
Katelynn Farmer ◽  
Robert Knight ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Evans Blue ◽  
Thermal Therapy ◽  
Female Rats ◽  
Brain Barrier ◽  
Gadolinium Contrast ◽  
Dce Mri ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Bbb Opening

Abstract Laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas, brain tumors in eloquent regions and/or otherwise inaccessible. Following reports of persistent peri-ablation blood-brain barrier (BBB) opening in humans, we examined this phenomenon using a rat glioblastoma model. Athymic female rats were implanted with U251 tumor cells in one brain hemisphere. Tumor growth was monitored using magnetic resonance imaging (MRI) and dynamic contrast enhanced (DCE)-MRI. When tumors reached about 4 mm in diameter, they were ablated under supervision of diffusion-weighted MRI using Visualase®, a clinical LITT system. Four rats were used as controls. Longitudinal MRI data were obtained before LITT, and at post-LITT 2 (n=9), 3 (n=3) and 4 (n=9) weeks. After the terminal MRI at each time point, rats were injected intravenously with fluorescent isothiocyanate dextran (FITC-dextran; 2000 kDa) and Evans Blue (68 kDa after binding to plasma albumin) and the brains immersion fixed in 10% paraformaldehyde. The brains were cut into 100 μM thick slices in a vibratome and examined for the distribution of the two fluorophores. All rats survived the LITT procedure. The sham controls showed increased tumor burden by 2 weeks and were sacrificed. DCE-MRI data and fluorescent data showed elevated BBB permeability in peri-ablation regions, with leakage of a gadolinium contrast on DCE-MRI and of Evans Blue, but not of FITC-dextran. Histology showed little tumor tissue at 2 weeks, but evidence of recurrence at ablation margins at later times. These data demonstrate that LITT is adaptable to rat glioma models and can be performed under MRI monitoring. Peri-ablation regions showed selective increase in BBB permeability acutely due to sublethal heating, but later increases in permeability may be due to tumor recurrence. We suggest this model is useful for examining the temporal and spatial development of peri-ablation BBB opening following LITT.

Abstract P189: AT 1 R-Dependent Blood-Brain Barrier Disruption Precedes Neuroinflammation In Age-Dependent Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kayla M Nist ◽  
Jesse Moreira ◽  
Richard D Wainford
Keyword(s):  
Blood Pressure ◽  
Blood Brain Barrier ◽  
Neural Control ◽  
Brain Barrier ◽  
Sprague Dawley ◽  
Control Center ◽  
Blood Brain Barrier Disruption ◽  
Sd Rats ◽  
Blood Brain ◽  
Age Dependent

AIM: We hypothesized paraventricular nucleus (PVN)-specific blood-brain barrier (BBB) dysfunction and neuroinflammation contribute to hypertension and sympathoexcitation that can be attenuated by an Angiotensin II Type 1 Receptor (AT 1 R)-dependent mechanism in the aging Sprague-Dawley (SD) rat. Methods: Naïve male SD rats aged 3-, 8- and 16-months-old (MO) (N=4-6/gp) were used in the following studies. Separate groups of 16 MO rats were administered losartan (21 days; s.c. 3 mg/kg/day) or hydrochlorothiazide (14 days; s.c. 4 mg/kg/day). Blood pressure (femoral cannulation) and plasma NE (ELISA) were assessed at end of study. In separate groups, BBB dysfunction was assessed via PVN FITC extravasation using intravascular co-infusion of FITC-Dextran (10 kDa) and rhodamine B isothiocyanate-Dextran (70 kDa). IHC/IF was performed in naive and losartan-treated rats for microglia (CD11b/c) and astrocytes (GFAP) in the PVN and subfornical organ (SFO). Results: Male SD rats develop HTN and sympathoexcitation with age. At 8 and 16 MO, rats exhibit PVN BBB dysfunction (increased FITC extravasation). However, only 16 MO rats exhibit significant PVN neuroinflammation (increased microglial activation and astrocyte reactivity). In the SFO, there is no evidence of age-dependent neuroinflammation. Losartan and HCTZ both significantly lower blood pressure to similar levels, however, only losartan significantly attenuates PVN BBB dysfunction and neuroinflammation. Conclusions: Within the PVN, a known neural control center, there are AT 1 R-dependent increases in PVN BBB disruption and neuroinflammation that we speculate contribute to hypertension in aging SD rats.

scholarly journals CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport

2020 ◽  
Vol 9 (10) ◽  
pp. 3236
Author(s):  
Luke Wainwright ◽  
Iain P. Hargreaves ◽  
Ana R. Georgian ◽  
Charles Turner ◽  
R. Neil Dalton ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Advanced Glycation Endproducts ◽  
Brain Barrier ◽  
High Dose ◽  
Blood Brain ◽  
Coq10 Deficiency ◽  
The Brain

Primary coenzyme Q10 (CoQ10) deficiency is unique among mitochondrial respiratory chain disorders in that it is potentially treatable if high-dose CoQ10 supplements are given in the early stages of the disease. While supplements improve peripheral abnormalities, neurological symptoms are only partially or temporarily ameliorated. The reasons for this refractory response to CoQ10 supplementation are unclear, however, a contributory factor may be the poor transfer of CoQ10 across the blood–brain barrier (BBB). The aim of this study was to investigate mechanisms of CoQ10 transport across the BBB, using normal and pathophysiological (CoQ10 deficient) cell culture models. The study identifies lipoprotein-associated CoQ10 transcytosis in both directions across the in vitro BBB. Uptake via SR-B1 (Scavenger Receptor) and RAGE (Receptor for Advanced Glycation Endproducts), is matched by efflux via LDLR (Low Density Lipoprotein Receptor) transporters, resulting in no “net” transport across the BBB. In the CoQ10 deficient model, BBB tight junctions were disrupted and CoQ10 “net” transport to the brain side increased. The addition of anti-oxidants did not improve CoQ10 uptake to the brain side. This study is the first to generate in vitro BBB endothelial cell models of CoQ10 deficiency, and the first to identify lipoprotein-associated uptake and efflux mechanisms regulating CoQ10 distribution across the BBB. The results imply that the uptake of exogenous CoQ10 into the brain might be improved by the administration of LDLR inhibitors, or by interventions to stimulate luminal activity of SR-B1 transporters.

The effect of interleukin-2 on the blood-brain barrier in the 9L gliosarcoma rat model

1989 ◽  
Vol 70 (1) ◽  
pp. 92-96 ◽  
Author(s):  
Joseph T. Alexander ◽  
Stephen C. Saris ◽  
Edward H. Oldfield
Keyword(s):  
Blood Brain Barrier ◽  
Interleukin 2 ◽  
Brain Barrier ◽  
High Dose ◽  
Normal Brain ◽  
Content Type ◽  
Tumor Bearing ◽  
Blood Brain ◽  
Significant Difference ◽  
Fine Print

✓ Carbon-14-labeled aminoisobutyric acid was used to determine local blood-to-tissue transfer constants in 22 Fischer rats with intracerebral 9L gliosarcomas that received either high-dose parenteral interleukin-2 (IL-2) or a control injection. In tumor and peritumoral tissue, the transfer constants in the IL-2-treated animals (89.6 ± 14.6 and 35.8 ± 6.0, respectively, mean ± standard error of the mean) were larger (p < 0.05) than in control animals (61.4 ± 6.4 and 14.6 ± 2.2, respectively). In contrast, in normal frontal and occipital tissue contralateral to the tumor-bearing hemisphere, there was no significant difference between the transfer constants in IL-2-treated and control animals. Furthermore, treatment of animals with IL-2 excipient caused no change in permeability as compared to animals treated with Hanks' balanced salt solution. Parenteral injection of IL-2 increases blood-brain barrier disruption in tumor-bearing rat brain but does not increase the vascular permeability of normal brain. Methods to prevent this increased tumor vessel permeability are required before parenteral IL-2 can be used safely for the treatment of primary or metastatic brain tumors.

Sign in / Sign up

Export Citation Format

Share Document