Ethanolamine: A Potential Promoiety with Additional Effects in the Brain

2020 ◽  
Vol 19 ◽  
Author(s):  
Asfree Gwanyanya ◽  
Christie Nicole Godsmark ◽  
Roisin Kelly-Laubscher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Design ◽  
Cell Signaling ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
The Central Nervous System ◽  
Bioactive Molecule ◽  
Positive Functions ◽  
The Brain

Abstract: Ethanolamine is a bioactive molecule found in several cells, including those in the central nervous system (CNS). In the brain, ethanolamine and ethanolamine-related molecules have emerged as prodrug moieties that can promote drug movement across the blood-brain barrier. This improvement in the ability to target drugs to the brain may also mean that in the process ethanolamine concentrations in the brain are increased enough for ethanolamine to exert its own neurological ac-tions. Ethanolamine and its associated products have various positive functions ranging from cell signaling to molecular storage, and alterations in their levels have been linked to neurodegenerative conditions such as Alzheimer’s disease. This mini-review focuses on the effects of ethanolamine in the CNS and highlights the possible implications of these effects for drug design.

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 Blood-brain barrier-restricted translocation of Toxoplasma gondii from cortical capillaries

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gabriela C Olivera ◽  
Emily C Ross ◽  
Christiane Peuckert ◽  
Antonio Barragan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Toxoplasma Gondii ◽  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Cortical Capillaries ◽  
The Brain

The cellular barriers of the central nervous system proficiently protect the brain parenchyma from infectious insults. Yet, the single-celled parasite Toxoplasma gondii commonly causes latent cerebral infection in humans and other vertebrates. Here, we addressed the role of the cerebral vasculature in the passage of T. gondii to the brain parenchyma. Shortly after inoculation in mice, parasites mainly localized to cortical capillaries, in preference over post-capillary venules, cortical arterioles or meningeal and choroidal vessels. Early invasion to the parenchyma (days 1-5) occurred in absence of a measurable increase in blood-brain barrier (BBB) permeability, perivascular leukocyte cuffs or hemorrhage. However, sparse focalized permeability elevations were detected adjacently to replicative parasite foci. Further, T. gondii triggered inflammatory responses in cortical microvessels and endothelium. Pro- and anti-inflammatory treatments of mice with LPS and hydrocortisone, respectively, impacted BBB permeability and parasite loads in the brain parenchyma. Finally, pharmacological inhibition or Cre/loxP conditional knockout of endothelial focal adhesion kinase (FAK), a BBB intercellular junction regulator, facilitated parasite translocation to the brain parenchyma. The data reveal that the initial passage of T. gondii to the central nervous system occurs principally across cortical capillaries. The integrity of the microvascular BBB restricts parasite transit, which conversely is exacerbated by the inflammatory response.

scholarly journals The blood–brain barrier

2020 ◽  
pp. S32-S34
Author(s):  
S Dingezweni
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transport Systems ◽  
Barrier Structure ◽  
Waste Products ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

The blood–brain barrier (BBB) is a dynamic barrier essential for central nervous system interstitial fluid separation from circulating blood. This dynamic separation ensures maintenance of neuronal microenvironment homeostasis against that of the everchanging in solutes and toxin concentration in circulating blood. The blood–brain barrier structure is complex, it has multiple contributors, such as specialised blood microvascular endothelium, neurons, astrocytes and pericytes. Transfer of essential nutrients to the brain and waste products from the brain to circulating blood is tightly regulated and facilitated by a large surface area and specialised transport systems. It is not only the physical characteristics of the barrier that assist in maintenance of neuronal microenvironment, biochemical substances and the high trans endothelial electrical resistance also play a major role. Circumventricular organs are those parts of the central nervous system lacking the blood–brain barrier. These are essential for optimum central nervous system interaction with circulating blood directly or using neurotransmitters. Primary or secondary central nervous system pathological states, such as infective and noninfective causes, directly or indirectly induce biochemical mediators that may disrupt and alter blood–brain barrier structure and function. Understanding of the blood–brain barrier anatomy and physiology assists in developing treatment methods to overcome degenerative and pathological states negatively affecting the central nervous system.

scholarly journals Central nervous system diseases associated with blood brain barrier breakdown - A Comprehensive update of existing literatures

2020 ◽  
Vol 4 (2) ◽  
pp. 053-062
Author(s):  
Dutta Rajib
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Barrier Breakdown ◽  
The Brain ◽  
Blood Brain Barrier Breakdown

Blood vessels that supply and feed the central nervous system (CNS) possess unique and exclusive properties, named as blood–brain barrier (BBB). It is responsible for tight regulation of the movement of ions, molecules, and cells between the blood and the brain thereby maintaining controlled chemical composition of the neuronal milieu required for appropriate functioning. It also protects the neural tissue from toxic plasma components, blood cells and pathogens from entering the brain. In this review the importance of BBB and its disruption causing brain pathology and progression to different neurological diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) etc. will be discussed.

scholarly journals Cryptococcal Yeast Cells Invade the Central Nervous System via Transcellular Penetration of the Blood-Brain Barrier

2004 ◽  
Vol 72 (9) ◽  
pp. 4985-4995 ◽  
Author(s):  
Yun C. Chang ◽  
Monique F. Stins ◽  
Michael J. McCaffery ◽  
Georgina F. Miller ◽  
Dan R. Pare ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Yeast Cells ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT Cryptococcal meningoencephalitis develops as a result of hematogenous dissemination of inhaled Cryptococcus neoformans from the lung to the brain. The mechanism(s) by which C. neoformans crosses the blood-brain barrier (BBB) is a key unresolved issue in cryptococcosis. We used both an in vivo mouse model and an in vitro model of the human BBB to investigate the cryptococcal association with and traversal of the BBB. Exposure of human brain microvascular endothelial cells (HBMEC) to C. neoformans triggered the formation of microvillus-like membrane protrusions within 15 to 30 min. Yeast cells of C. neoformans adhered to and were internalized by the HBMEC, and they crossed the HBMEC monolayers via a transcellular pathway without affecting the monolayer integrity. The histopathology of mouse brains obtained after intravenous injection of C. neoformans showed that the yeast cells either were associated with endothelial cells or escaped from the brain capillary vessels into the neuropil by 3 h. C. neoformans was found in the brain parenchyma away from the vessels by 22 h. Association of C. neoformans with the choroid plexus, however, was not detected during up to 10 days of observation. Our findings indicate that C. neoformans cells invade the central nervous system by transcellular crossing of the endothelium of the BBB.

scholarly journals A Nanomule Peptide-siRNA Conjugate that Traverses the Intact Blood Brain Barrier and Attenuates Stroke

2019 ◽  
Author(s):  
Brett A. Eyford ◽  
Chaahat S.B. Singh ◽  
Thomas Abraham ◽  
Lonna Munro ◽  
Kyung Bok Choi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Significant Protection ◽  
Amino Acid Peptide ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

AbstractThe blood-brain barrier (BBB), hinders the distribution of therapeutics, intended for treatment of diseases of the brain. A twelve-amino acid peptide, termed MTfp, was derived from MTf, and retains the ability to cross the BBB intact and ferry cargo into intacellular organelles within neurons, glia and microglia in the brain. A novel MTfp-siRNA peptide-oligonucleotide conjugate (POC), directed against NOX4, a gene known to potentiate ischemic stroke, was chemically synthesized. The MTfp-NOX4 siRNA POC traversed the BBB, resulting in the knockdown of NOX4 expression in the brain. Following induction of ischemic stroke, animals treated with the POC exhibited significantly smaller infarcts; accompanied by significant protection against neurological deterioration and improved recovery. The data demonstrates that the MTfp portion, of this novel POC, can facilitate BBB transcytosis; where the siRNA moiety can elicit effective therapeutic knockdown of a gene associated with a disease of the central nervous system (CNS). This is a general platform to transport therapeutics to the CNS and thereby, offers new avenues for potential treatments of neuropathologies that are currently refractory to existing therapies.

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