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 Noncovalent Strategy with Cell-Penetrating Peptides to Facilitate the Brain Delivery of Insulin through the Blood–Brain Barrier

2018 ◽  
Vol 41 (4) ◽  
pp. 546-554 ◽  
Author(s):  
Noriyasu Kamei ◽  
Ai Yamaoka ◽  
Yukiko Fukuyama ◽  
Rei Itokazu ◽  
Mariko Takeda-Morishita
Keyword(s):  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Blood Brain ◽  
Cell Penetrating ◽  
The Brain

Accessing the Blood-Brain Barrier to Treat Brain Disorders

2019 ◽  
Vol 9 (3) ◽  
pp. 198-209
Author(s):  
M. Sureshkumar ◽  
A. Pandian
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Low Molecular Weight ◽  
Brain Disorders ◽  
Permeable Membrane ◽  
Drug Molecules ◽  
Blood Brain ◽  
Therapeutic Molecules ◽  
Pass Through ◽  
The Brain

: Crossing the blood-brain barrier (BBB) and treating brain disorders by delivering therapeutic agents to specific regions of the brain is a challenge. The BBB, naturally evolved, protective physiological barrier acts as a selective permeable membrane in such a way that it allows only nonionic molecules and molecules of low molecular weight to pass through. Treating brain tumor has become a great challenge as the drug molecules of larger size are not able to cross the BBB and reach the target site. The incompetence of techniques for brain-specific delivery of therapeutic molecules has led researchers to increasingly explore the diagnosis and treatment of disorders incurable with present techniques. This article is to discuss the various techniques or methods to deliver drugs to the brain crossing the BBB.

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.

scholarly journals Combination of cell-penetrating peptides with nanomaterials for the potential therapeutics of central nervous system disorders: a review

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Zhang ◽  
Pan Guo ◽  
Zhe Ma ◽  
Peng Lu ◽  
Dereje Kebebe ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Human Life ◽  
Scientific Basis ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Cns Diseases ◽  
Blood Brain ◽  
Cell Penetrating

AbstractAlthough nanomedicine have greatly developed and human life span has been extended, we have witnessed the soared incidence of central nervous system (CNS) diseases including neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), ischemic stroke, and brain tumors, which have severely damaged the quality of life and greatly increased the economic and social burdens. Moreover, partial small molecule drugs and almost all large molecule drugs (such as recombinant protein, therapeutic antibody, and nucleic acid) cannot cross the blood–brain barrier. Therefore, it is especially important to develop a drug delivery system that can effectively deliver therapeutic drugs to the central nervous system for the treatment of central nervous system diseases. Cell penetrating peptides (CPPs) provide a potential strategy for the transport of macromolecules through the blood–brain barrier. This study analyzed and summarized the progress of CPPs in CNS diseases from three aspects: CPPs, the conjugates of CPPs and drug, and CPPs modified nanoparticles to provide scientific basis for the application of CPPs for CNS diseases.

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.

scholarly journals Cell-Penetrating Peptides Selectively Cross the Blood-Brain Barrier In Vivo

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0139652 ◽  
Author(s):  
Sofie Stalmans ◽  
Nathalie Bracke ◽  
Evelien Wynendaele ◽  
Bert Gevaert ◽  
Kathelijne Peremans ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cell Penetrating

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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