scholarly journals Gyógyszertranszporterek szerepe a központi idegrendszerben

2016 ◽  
Vol 157 (10) ◽  
pp. 370-378
Author(s):  
Franciska Erdő ◽  
Csilla Temesszentandrási-Ambrus ◽  
Erzsébet Beéry
Keyword(s):  
Blood Brain Barrier ◽  
Cell Types ◽  
Brain Barrier ◽  
Transporter Proteins ◽  
Atp Binding Cassette Transporter ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Solute Carrier Transporters ◽  
Different Cell Types ◽  
The Brain

Although the presence of blood–brain barrier in the mammalian organisms was discovered in the early 1900s, its precise structure and the drug transporter proteins localized in the blood–brain barrier were identified only in the last decades. Beside the ATP-binding cassette transporter proteins responsible for the protection of the brain, the Solute Carrier transporters play also an important role in the function of the central nervous system by its feeding, energy supply and cleaning function during the metabolism. This review provides an overview on the main types of transporters located in the brain, on their localization in different cell types and the main techniques for their investigation. In the second part of this article various neurodegenerative disorders and the pathology-related transporter proteins are presented. In the light of recent experimental results new therapeutic strategies may come into the focus of research for the treatment of disorders currently without effective therapy. Orv. Hetil., 2016, 157(10), 370–378.

The Blood brain-barrier and its role in Alzheimer’s disease

Neuroforum ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. A197-A205 ◽  
Author(s):  
Steffen E. Storck ◽  
Claus U. Pietrzik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Cell Types ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Different Cell Types ◽  
The Brain ◽  
Brain Homeostasis

Abstract The blood brain-barrier (BBB), built up by the interaction of different cell types in vessels of the brain, is essential for brain homeostasis. As a gatekeeper of the central nervous system (CNS), the BBB controls the exchange of molecules between brain and blood. In many neurodegenerative diseases including Alzheimer’s disease (AD) the BBB show alterations which impair brain function and promote neurodegeneration. As an important elimination route for neurotoxic amyloid-beta (Aβ), the BBB is crucial for the healthy brain by regulating the concentration of soluble Aβ in the interstitial fluid (ISF) in the brain. Here, we discuss the composition and distinctive physiological features of CNS vasculature and the pathological alterations that are present in AD and disturb BBB function.

scholarly journals A vér–agy gát működése, öregedése és diszfunkciója. Átjutás a barrieren

2016 ◽  
Vol 157 (51) ◽  
pp. 2019-2027
Author(s):  
Franciska Erdő ◽  
Barbara Hutka ◽  
László Dénes
Keyword(s):  
Blood Brain Barrier ◽  
Morphological Changes ◽  
Cell Types ◽  
Brain Barrier ◽  
Molecular Systems ◽  
Dna Mutation ◽  
System Protection ◽  
Blood Brain ◽  
Different Cell Types ◽  
The Brain

Abstract: The blood–brain barrier is an interface between the circulation and brain. It is responsible for the homeostasis of central nervous system, protection and feeding of the brain and for providing the conditions for fine regulation of neurons. The coordinated function of different cell types and the regulated expression of molecular systems make possible the functionality of blood–brain barrier. However, this complex system can be broken due to different insults with a consequence of appearance of elevated levels of unwanted exogenous and endogenous molecules in the brain involved in the pathomechanisms of several disorders. The most important risk factor for the damage of blood–brain barrier is the aging itself, which causes disruption of the barrier through DNA mutation, oxidative stress and release of inflammatory mediators. Although the physiological aging is accompanied by morphological changes, the dysfunction of membrane transporters could also lead to neurodegenerative disorders. Structure, function and breakdown of the blood–brain barrier and the possibilities to cross it, are presented. Orv. Hetil., 2016, 157(51), 2019–2027.

Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats

2007 ◽  
Vol 292 (5) ◽  
pp. R1881-R1892 ◽  
Author(s):  
Sharon Hom ◽  
Melissa A. Fleegal ◽  
Richard D. Egleton ◽  
Christopher R. Campos ◽  
Brian T. Hawkins ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Ion Transporter ◽  
Transporter Proteins ◽  
Wky Rats ◽  
Blood Brain ◽  
Hypertension Development ◽  
The Brain

Hypertension is involved in the exacerbation of stroke. It is unclear how blood-brain barrier (BBB) tight-junction (TJ) and ion transporter proteins critical for maintaining brain homeostasis contribute to cerebral infarction during hypertension development. In the present study, we investigated cerebral infarct volume following permanent 4-h middle cerebral artery occlusion (MCAO) and characterized the expression of BBB TJ and ion transporter proteins in brain microvessels of spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) rats at 5 wk (prehypertension), 10 wk (early-stage hypertension), and 15 wk (later-stage hypertension) of age. Hypertensive SHR show increased infarct volume following MCAO compared with WKY control rats. BBB TJ and ion transporter proteins, known to contribute to edema and fluid volume changes in the brain, show differential protein expression patterns during hypertension development. Western blot analysis of TJ protein zonula occludens-2 (ZO-2) showed decreased expression, while ion transporter, Na+/H+ exchanger 1 (NHE-1), was markedly increased in hypertensive SHR. Expression of TJ proteins ZO-1, occludin, actin, claudin-5, and Na+-K+-2Cl− cotransporter remain unaffected in SHR compared with control. Selective inhibition of NHE-1 using dimethylamiloride significantly attenuated ischemia-induced infarct volume in hypertensive SHR following MCAO, suggesting a novel role for NHE-1 in the brain in the regulation of ischemia-induced infarct volume in SHR.

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 Blood-brain barrier behavior during temporary concussion

1960 ◽  
Vol 198 (6) ◽  
pp. 1296-1298 ◽  
Author(s):  
Benedict Cassen ◽  
Richard Neff
Keyword(s):  
Central Nervous System ◽  
Blood Brain Barrier ◽  
Normal Activity ◽  
Brain Barrier ◽  
Electrolyte Balance ◽  
Barrier Membranes ◽  
Phosphate Ions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

Experimental evidence is obtained that, coincident with a state of not too severe concussion, the blood-brain barrier system becomes more permeable to phosphate ions. The permeability returns to normal when the animal recovers and shows normal activity. Arguments are presented in favor of the hypothesis that dysfunction of the central nervous system during concussion is related to a disturbed electrolyte balance in the fluids of the brain caused by a piezochemical disturbance of the blood-brain barrier membranes (presumably the astropods of the astrocytic cells).

scholarly journals Photostimulation of Extravasation of Beta-Amyloid through the Model of Blood-Brain Barrier

Electronics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1056
Author(s):  
Ekaterina Zinchenko ◽  
Maria Klimova ◽  
Aysel Mamedova ◽  
Ilana Agranovich ◽  
Inna Blokhina ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Beta Amyloid ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Cervical Lymph Nodes ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Vitro Model ◽  
The Brain

Alzheimer’s disease (AD) is an incurable pathology associated with progressive decline in memory and cognition. Phototherapy might be a new promising and alternative strategy for the effective treatment of AD, and has been actively discussed over two decades. However, the mechanisms of therapeutic photostimulation (PS) effects on subjects with AD remain poorly understood. The goal of this study was to determine the mechanisms of therapeutic PS effects in beta-amyloid (Aβ)-injected mice. The neurological severity score and the new object recognition tests demonstrate that PS 9 J/cm2 attenuates the memory and neurological deficit in mice with AD. The immunohistochemical assay revealed a decrease in the level of Aβ in the brain and an increase of Aβ in the deep cervical lymph nodes obtained from mice with AD after PS. Using the in vitro model of the blood-brain barrier (BBB), we show a PS-mediated decrease in transendothelial resistance and in the expression of tight junction proteins as well an increase in the BBB permeability to Aβ. These findings suggest that a PS-mediated BBB opening and the activation of the lymphatic clearance of Aβ from the brain might be a crucial mechanism underlying therapeutic effects of PS in mice with AD. These pioneering data open new strategies in the development of non-pharmacological methods for therapy of AD and contribute to a better understanding of the PS effects on the central nervous system.

scholarly journals Tembusu Virus entering the central nervous system caused nonsuppurative encephalitis without disrupting the blood-brain barrier

2021 ◽  
Author(s):  
Sheng Yang ◽  
Yufei Huang ◽  
Yonghong Shi ◽  
Xuebing Bai ◽  
Ping Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Neurological Symptoms ◽  
Brain Barrier ◽  
Poultry Industry ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Tembusu Virus ◽  
The Brain

Tembusu Virus (TMUV) is an emerging and re-emerging zoonotic pathogen that adversely affects poultry industry in recent years. TMUV disease is characterized by nonsuppurative encephalitis in ducklings. The duckling infection model was established to study the mechanism of TMUV crossing the blood-brain barrier (BBB) into the central nervous system (CNS). Here, we showed that no obvious clinical symptoms and enhancement of BBB permeability occurred at the early stage of infection (3∼5 dpi). While simultaneously virus particles were observed by transmission electron microscopy in the brain, inducing the accumulation of inflammatory cytokines. Neurological symptoms and disruption of BBB appeared at the intermediate stage of infection (7∼9 dpi). It was confirmed that TMUV could survive and propagate in brain microvascular endothelial cells (BMECs), but did not affect the permeability of BBB in vivo and in vitro at an early date. In conclusion, TMUV enters the CNS then causes encephalitis, and finally destruct the BBB, which may be due to the direct effect of TMUV on BMECs and the subsequent response of “inflammatory storm”. IMPORTANCE The TMUV disease has caused huge losses to the poultry industry in Asia, which is potentially harmful to public health. Neurological symptoms and their sequelae are the main characters of this disease. However, the mechanism of how this virus enters the brain and causes encephalitis is unclear. In this study, we confirmed that the virus entered the CNS and then massively destroyed BBB and the BBB damage was closely associated with the subsequent outbreak of inflammation. TMUV may enter the CNS through the transcellular and “Trojan horse” pathways. These findings can fill the knowledge gap in the pathogenesis of TMUV-infected poultry and be benefit for the treatment of TMUV disease. What’s more, TMUV is a representative to study the infection of avian flavivirus. Therefore, our studies have significances both for understanding of the full scope of mechanisms of TMUV and other flavivirus infection, and conceivably, for therapeutics.

Iodide and thiocyanate efflux from brain following injection into rat caudate nucleus

1978 ◽  
Vol 235 (4) ◽  
pp. F331-F337 ◽  
Author(s):  
H. F. Cserr ◽  
B. J. Berman
Keyword(s):  
Caudate Nucleus ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Common Mechanism ◽  
Efflux System ◽  
Guide Cannula ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Loading Estimates ◽  
The Brain

Mechanisms and pathways of 125I and 35SCN efflux from the brain were investigated in anesthetized rats. Tracers were injected into the caudate nucleus through a guide cannula implanted 1 wk previously and concentrations of isotope in brain and cerebrospinal fluid (CSF) were determined at various times after injection. 125I clearance from the brain followed a single exponential curve. In control rats 36.2% of the 125I remained in the brain 30 min after injection and 60.4% in rats pretreated with perchlorate. Comparable values for 35SCN were 25.8% in control rats, 41.0% with perchlorate, and 39.7% with iodide loading. Estimates of 125I and 35SCN effluxes from the brain via the blood-brain barrier and CSF pathways suggest that greater than 95% of efflux crosses the blood-brain barrier. These results indicate that 1)iodide and thiocyanate are transported across the blood-brain barrier by a common mechanism, and 2) this efflux system is an important factor in the control of the distributions of iodide and thiocyanate in the central nervous system.

Cell-Penetrating Peptides: As a Promising Theranostics Strategy to Circumvent the Blood-Brain Barrier for CNS Diseases

2020 ◽  
Vol 17 (5) ◽  
pp. 375-386 ◽  
Author(s):  
Behrang Shiri Varnamkhasti ◽  
Samira Jafari ◽  
Fereshteh Taghavi ◽  
Loghman Alaei ◽  
Zhila Izadi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Cns Disorders ◽  
Blood Brain ◽  
Cell Penetrating ◽  
Therapeutic Molecules ◽  
The Central Nervous System ◽  
Low Cytotoxicity ◽  
The Brain

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain.

scholarly journals PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 72 ◽  
Author(s):  
Gina P. Hoyos-Ceballos ◽  
Barbara Ruozi ◽  
Ilaria Ottonelli ◽  
Federica Da Ros ◽  
Maria Angela Vandelli ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Glycolic Acid ◽  
Plga Nanoparticles ◽  
Brain Barrier ◽  
Proof Of Concept ◽  
Brain Drug Delivery ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Research Challenge ◽  
The Brain

The treatment of diseases that affect the central nervous system (CNS) represents a great research challenge due to the restriction imposed by the blood–brain barrier (BBB) to allow the passage of drugs into the brain. However, the use of modified nanomedicines engineered with different ligands that can be recognized by receptors expressed in the BBB offers a favorable alternative for this purpose. In this work, a BBB-penetrating peptide, angiopep-2 (Ang–2), was conjugated to poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles through pre- and post-formulation strategies. Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.

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