scholarly journals CT Imaging and Spontaneous Behavior Analysis After Osmotic Blood-Brain Barrier Opening in Wistar Rat

2014 ◽  
pp. S529-S534 ◽  
Author(s):  
P. KOZLER ◽  
V. RILJAK ◽  
K. JANDOVÁ ◽  
J. POKORNÝ
Keyword(s):  
Locomotor Activity ◽  
Brain Edema ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Spontaneous Locomotor Activity ◽  
Brain Barrier ◽  
Male Rats ◽  
Blood Brain ◽  
Significant Difference ◽  
The Brain

In our previous experiments we demonstrated that osmotic opening of the blood brain barrier (BBB) in rats by administration of mannitol into the internal carotid artery leads to cerebral edema. The aim of this study was to confirm objectively the development of brain edema and determine whether it affects spontaneous locomotor activity in rats (SLA). Brain edema was verified by computer tomography (CT) examination of the brain and SLA was observed during open field test. Twenty four adult male rats were divided into four groups of six: (1) control animals (C), (2) controls with anesthesia (CA), (3) controls with sham surgery (CS), (4) experimental – osmotic opening of the BBB (MA). Osmotic BBB disruption manifested by reducing the density of brain tissue (hypodensity), suggesting a higher water content in the brain tissue. SLA was compared between C, CA, CS and MA groups and between MA and CA groups. Significant difference was found only between the control group and MA group. In the first 30 min of the examination, rats after the mannitol administration revealed a marked limitation of spontaneous locomotor activity. Experimental results demonstrated reduction of spontaneous locomotor activity in rats with induced brain edema.

scholarly journals Population pharmacokinetic approach for evaluation of treosulfan and its active monoepoxide disposition in plasma and brain on the basis of a rat model

2020 ◽  
Vol 72 (5) ◽  
pp. 1297-1309
Author(s):  
Dorota Danielak ◽  
Michał Romański ◽  
Anna Kasprzyk ◽  
Artur Teżyk ◽  
Franciszek Główka
Keyword(s):  
Blood Brain Barrier ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Estimation Method ◽  
Rat Plasma ◽  
Brain Barrier ◽  
Male Rats ◽  
Population Pharmacokinetic ◽  
Blood Brain ◽  
The Brain

Abstract Purpose Efficacy of treosulfan, used in the treatment of marrow disorders, depends on the activity of its monoepoxy—(EBDM) and diepoxy compounds. The study aimed to describe the pharmacokinetics of treosulfan and EBDM in the rat plasma and brain by means of mixed-effects modelling. Methods The study had a one-animal-per-sample design and included ninty-six 10-week-old Wistar rats of both sexes. Treosulfan and EBDM concentrations in the brain and plasma were measured by an HPLC–MS/MS method. The population pharmacokinetic model was established in NONMEM software with a first-order estimation method with interaction. Results One-compartment pharmacokinetic model best described changes in the concentrations of treosulfan in plasma, and EBDM concentrations in plasma and in the brain. Treosulfan concentrations in the brain followed a two-compartment model. Both treosulfan and EBDM poorly penetrated the blood–brain barrier (ratio of influx and efflux clearances through the blood–brain barrier was 0.120 and 0.317 for treosulfan and EBDM, respectively). Treosulfan plasma clearance was significantly lower in male rats than in females (0.273 L/h/kg vs 0.419 L/h/kg). Conclusions The developed population pharmacokinetic model is the first that allows the prediction of treosulfan and EBDM concentrations in rat plasma and brain. These results provide directions for future studies on treosulfan regarding the contribution of transport proteins or the development of a physiological-based model.

Solving the challenge of the blood–brain barrier to treat infections caused by Trypanosoma evansi: evaluation of nerolidol-loaded nanospheres in mice

Parasitology ◽  
2017 ◽  
Vol 144 (11) ◽  
pp. 1543-1550 ◽  
Author(s):  
MATHEUS D. BALDISSERA ◽  
CARINE F. SOUZA ◽  
ALINE A. BOLIGON ◽  
THIRSSA H. GRANDO ◽  
MARIÂNGELA F. DE SÁ ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Blood Brain Barrier ◽  
High Performance ◽  
Drug Efficacy ◽  
Trypanosoma Evansi ◽  
Brain Barrier ◽  
Active Principle ◽  
Diminazene Aceturate ◽  
Blood Brain ◽  
The Brain

SUMMARYDespite significant advances in therapies against Trypanosoma evansi, its effective elimination from the central nervous system (CNS) remains a difficult task. The incapacity of trypanocidal drugs to cross the blood–brain barrier (BBB) after systemic administrations makes the brain the main refuge area for T. evansi. Nanotechnology is showing great potential to improve drug efficacy, such as nerolidol-loaded nanospheres (N-NS). Thus, the aim of this study was to investigate whether the treatment with N-NS was able to cross the BBB and to eliminate T. evansi from the CNS. High-performance liquid chromatography revealed that N-NS can cross the BBB of T. evansi-infected mice, while free nerolidol (F-N) neither the trypanocidal drug diminazene aceturate (D.A.) were not detected in the brain tissue. Polymerase chain reaction revealed that 100% of the animals treated with N-NS were negatives for T. evansi in the brain tissue, while all infected animals treated with F-N or D.A. were positives. Thus, we concluded that nanotechnology improves the therapeutic efficacy of nerolidol, and enables the transport of its active principle through the BBB. In summary, N-NS treatment can eliminate the parasite from the CNS, and possesses potential to treat infected animals.

scholarly journals Signs of Myelin Impairment in Cerebrospinal Fluid After Osmotic Opening of the Blood-Brain Barrier in Rats

2015 ◽  
pp. S603-S608 ◽  
Author(s):  
P. KOZLER ◽  
O. SOBEK ◽  
J. POKORNÝ
Keyword(s):  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Blood Brain Barrier ◽  
Basic Protein ◽  
Brain Barrier ◽  
In Vivo Experiment ◽  
Blood Brain ◽  
Significant Difference ◽  
The Brain

A number of clinical neurological pathologies are associated with increased permeability of the blood brain barrier (BBB). Induced changes of the homeostatic mechanisms in the brain microenvironment lead among others to cellular changes in the CNS. The question was whether some of these changes can be induced by osmotic opening of BBB in an in vivo experiment and whether they can be detected in cerebrospinal fluid (CSF). CSF was taken via the suboccipital puncture from 10 healthy rats and six rats after the osmotic opening of the BBB. In all 16 animals, concentration of myelin basic protein (MBP ng/ml), Neuron-specific enolase (NSE ng/ml) and Tau-protein (Tau pg/ml) were determined in CSF by ELISA. Values in both groups were statistically evaluated. Significant difference between the control and experimental group was revealed only for the concentration of myelin basic protein (p<0.01). The presented results indicate that osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions of the brain leads to a damage of myelin, without impairment of neurons or their axons.

scholarly journals Empirical and Theoretical Characterization of the Diffusion Process of Different Gadolinium-Based Nanoparticles within the Brain Tissue after Ultrasound-Induced Permeabilization of the Blood-Brain Barrier

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Allegra Conti ◽  
Rémi Magnin ◽  
Matthieu Gerstenmayer ◽  
Nicolas Tsapis ◽  
Erik Dumont ◽  
...  
Keyword(s):  
Diffusion Process ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Diffusion Coefficients ◽  
Brain Barrier ◽  
Apparent Diffusion Coefficients ◽  
Blood Brain ◽  
The Brain ◽  
And Diffusion

Low-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the diffusion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. Three compounds were tested (MultiHance, Gadovist, and Dotarem). We characterized their diffusion through in vivo experimental tests supported by theoretical models. Specifically, by estimation of the free diffusion coefficients from in vitro studies and of apparent diffusion coefficients from in vivo experiments, we have assessed tortuosity in the right striatum of 9 Sprague Dawley rats through a model correctly describing both vascular permeability as a function of time and diffusion processes occurring in the brain tissue. This model takes into account acoustic pressure, particle size, blood pharmacokinetics, and diffusion rates. Our model is able to fully predict the result of a FUS-induced BBB opening experiment at long space and time scales. Recovered values of tortuosity are in agreement with the literature and demonstrate that our improved model allows us to assess that the chosen permeabilization protocol preserves the integrity of the brain tissue.

Potential Regulation Mechanisms of P-gp in the Blood-Brain Barrier in Hypoxia

2019 ◽  
Vol 25 (10) ◽  
pp. 1041-1051 ◽  
Author(s):  
Yidan Ding ◽  
Rong Wang ◽  
Jianchun Zhang ◽  
Anpeng Zhao ◽  
Hui Lu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Signal Pathways ◽  
Blood Brain ◽  
Sphingosine 1 Phosphate ◽  
Capillary Endothelial Cells ◽  
The Brain ◽  
Expression And Activity

The blood-brain barrier (BBB) is a barrier of the central nervous system (CNS), which can restrict the free exchange of substances, such as toxins and drugs, between cerebral interstitial fluid and blood, keeping the relative physiological stabilization. The brain capillary endothelial cells, one of the structures of the BBB, have a variety of ATP-binding cassette transporters (ABC transporters), among which the most widely investigated is Pglycoprotein (P-gp) that can efflux numerous substances out of the brain. The expression and activity of P-gp are regulated by various signal pathways, including tumor necrosis factor-&#945; (TNF-&#945;)/protein kinase C-&#946; (PKC- &#946;)/sphingosine-1-phosphate receptor 1 (S1P), vascular endothelial growth factor (VEGF)/Src kinase, etc. However, it remains unclear how hypoxic signaling pathways regulate the expression and activity of P-gp in brain microvascular endothelial cells. According to previous research, hypoxia affects the expression and activity of the transporter. If the transporter is up-regulated, some drugs enter the brain&#039;s endothelial cells and are pumped back into the blood by transporters such as P-gp before they enter the brain tissue, consequently influencing the drug delivery in CNS; if the transporter is down-regulated, the centrally toxic drug would enter the brain tissue and cause serious adverse reactions. Therefore, studying the mechanism of hypoxia-regulating P-gp can provide an important reference for the treatment of CNS diseases with a hypoxia/reoxygenation (H/R) component. This article summarized the mechanism of regulation of P-gp in BBB in normoxia and explored that of hypoxia.

Road From Nose to Brain for Treatment of Alzheimer: The Bumps and Humps

2020 ◽  
Vol 19 (9) ◽  
pp. 663-675
Author(s):  
Rajesh Kumar ◽  
Monica Gulati ◽  
Sachin Kumar Singh ◽  
Deepika Sharma ◽  
Omji Porwal
Keyword(s):  
Drug Delivery ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Nasal Delivery ◽  
Brain Barrier ◽  
Nasal Drug Delivery ◽  
Blood Brain ◽  
Routes Of Drug Administration ◽  
Alternative Routes ◽  
The Brain

: Vulnerability of the brain milieu to even the subtle changes in its normal physiology is guarded by a highly efficient blood brain barrier. A number of factors i.e. molecular weight of the drug, its route of administration, lipophilic character etc. play a significant role in its sojourn through the blood brain barrier (BBB) and limit the movement of drug into brain tissue through BBB. To overcome these problems, alternative routes of drug administration have been explored to target the drugs to brain tissue. Nasal route has been widely reported for the administration of drugs for treatment of Alzheimer. In this innovative approach, the challenge of BBB is bypassed. Through this route, both the larger as well as polar molecules can be made to reach the brain tissues. Generally, these systems are either pH dependent or temperature dependent. Results: The present review highlights the anatomy of nose, mechanisms of drug delivery from nose to brain, critical factors in the formulation of nasal drug delivery system, nasal formulations of various drugs that have been tried for their nasal delivery for treatment of Alzheimer. Conclusion: It also dives deep to understand the factors that contribute to the success of such formulations to carve out a direction for this niche area to be explored further.

scholarly journals Preparation of Silica Nanoparticles Loaded with Nootropics and TheirIn VivoPermeation through Blood-Brain Barrier

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Josef Jampilek ◽  
Kamil Zaruba ◽  
Michal Oravec ◽  
Martin Kunes ◽  
Petr Babula ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Microscopic Analysis ◽  
Brain Perfusion ◽  
Brain Barrier ◽  
Bulk Materials ◽  
Drug Substances ◽  
Blood Brain ◽  
The Brain

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of anin vivomodel of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.

scholarly journals Non-thermal Electroporation Ablation of Epileptogenic Zones Stops Seizures in Mice While Providing Reduced Vascular Damage and Accelerated Tissue Recovery

2021 ◽  
Vol 15 ◽  
Author(s):  
Emma Acerbo ◽  
Sawssan Safieddine ◽  
Pascal Weber ◽  
Boris Botzanowski ◽  
Florian Missey ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Thermal Ablation ◽  
Neural Tissue ◽  
Brain Barrier ◽  
Seizure Freedom ◽  
Surgical Morbidity ◽  
Invasive Approach ◽  
Blood Brain ◽  
The Brain

In epilepsy, the most frequent surgical procedure is the resection of brain tissue in the temporal lobe, with seizure-free outcomes in approximately two-thirds of cases. However, consequences of surgery can vary strongly depending on the brain region targeted for removal, as surgical morbidity and collateral damage can lead to significant complications, particularly when bleeding and swelling are located near delicate functional cortical regions. Although focal thermal ablations are well-explored in epilepsy as a minimally invasive approach, hemorrhage and edema can be a consequence as the blood-brain barrier is still disrupted. Non-thermal irreversible electroporation (NTIRE), common in many other medical tissue ablations outside the brain, is a relatively unexplored method for the ablation of neural tissue, and has never been reported as a means for ablation of brain tissue in the context of epilepsy. Here, we present a detailed visualization of non-thermal ablation of neural tissue in mice and report that NTIRE successfully ablates epileptic foci in mice, resulting in seizure-freedom, while causing significantly less hemorrhage and edema compared to conventional thermal ablation. The NTIRE approach to ablation preserves the blood-brain barrier while pathological circuits in the same region are destroyed. Additionally, we see the reinnervation of fibers into ablated brain regions from neighboring areas as early as day 3 after ablation. Our evidence demonstrates that NTIRE could be utilized as a precise tool for the ablation of surgically challenging epileptogenic zones in patients where the risk of complications and hemorrhage is high, allowing not only reduced tissue damage but potentially accelerated recovery as vessels and extracellular matrix remain intact at the point of ablation.

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