scholarly journals The Angiotensin II Type 2 Receptor, a Target for Protection and Regeneration of the Peripheral Nervous System?

2021 ◽  
Vol 14 (3) ◽  
pp. 175
Author(s):  
Aurore Danigo ◽  
Amandine Rovini ◽  
Flavien Bessaguet ◽  
Hichem Bouchenaki ◽  
Amandine Bernard ◽  
...  
Keyword(s):  
Nervous System ◽  
Angiotensin Ii ◽  
Peripheral Nervous System ◽  
Neuroprotective Effects ◽  
Pharmacological Studies ◽  
The Central Nervous System ◽  
G Protein Coupled

Preclinical evidence, accumulated over the past decade, indicates that the angiotensin II type 2 receptor (AT2R) stimulation exerts significant neuroprotective effects in various animal models of neuronal injury, notably in the central nervous system. While the atypical G protein-coupled receptor superfamily nature of AT2R and its related signaling are still under investigation, pharmacological studies have shown that stimulation of AT2R leads to neuritogenesis in vitro and in vivo. In this review, we focus on the potential neuroprotective and neuroregenerative roles of AT2R specifically in the peripheral nervous system (PNS). The first section describes the evidence for AT2R expression in the PNS and highlights current controversies concerning the cellular distribution of the receptor. The second section focuses on AT2R signaling implicated in neuronal survival and in neurite outgrowth. The following sections review the relatively few preclinical studies highlighting the putative neuroprotective and neuroregenerative effects of AT2R stimulation in the context of peripheral neuropathy.

scholarly journals Emerging Roles of Exosomes in Huntington’s Disease

2021 ◽  
Vol 22 (8) ◽  
pp. 4085
Author(s):  
Hanadi Ananbeh ◽  
Petr Vodicka ◽  
Helena Kupcova Skalnikova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Cell Types ◽  
Neuroprotective Effects ◽  
The Central Nervous System

Huntington’s disease (HD) is a rare hereditary autosomal dominant neurodegenerative disorder, which is caused by expression of mutant huntingtin protein (mHTT) with an abnormal number of glutamine repeats in its N terminus, and characterized by intracellular mHTT aggregates (inclusions) in the brain. Exosomes are small extracellular vesicles that are secreted generally by all cell types and can be isolated from almost all body fluids such as blood, urine, saliva, and cerebrospinal fluid. Exosomes may participate in the spreading of toxic misfolded proteins across the central nervous system in neurodegenerative diseases. In HD, such propagation of mHTT was observed both in vitro and in vivo. On the other hand, exosomes might carry molecules with neuroprotective effects. In addition, due to their capability to cross blood-brain barrier, exosomes hold great potential as sources of biomarkers available from periphery or carriers of therapeutics into the central nervous system. In this review, we discuss the emerging roles of exosomes in HD pathogenesis, diagnosis, and therapy.

Design, fabrication, and testing of a bioprinted nerve graft

2016 ◽  
Author(s):  
◽  
Christopher M. Owens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Graft ◽  
Loss Of Function ◽  
Vitro Assay ◽  
Central Nervous System Damage ◽  
In Vivo Animal Model ◽  
The Central Nervous System

Injuries to nerves vary in their consequences, from weakened sensation and motor function to partial or complete paralysis. In the latter case, affecting about twenty thousand Americans yearly, the injury is debilitating and results in a significant decrease in quality of life. Currently there is no effective treatment for damage to the central nervous system, in particular the spinal cord. Compared to the injuries to the central nervous system, damage in the peripheral nerves, is more common, with about sixty thousand occurrences annually. The cost of associated surgical procedures and due to loss of function is in the billions. In this thesis we present work towards the construction and testing of a fully cellular, patented nerve graft, one amongst the first of its kind. For the fabrication of the graft we are the first to employ bioprinting (either implemented through a special purpose 3D bioprinter or manually), a novel tissue engineering method rapidly gaining acceptance and utility. We first review the status of bioprinting. We then detail the fabrication process. Next we report on the testing of the graft in an in vivo animal model through electrophysiology and histology. This is followed by the introduction of a novel in vitro model, aimed at providing a fast, inexpensive and reliable method to test engineered nerve grafts. We describe our work on the optimization of the in vitro assay and then the testing of the graft using the optimized assay. We conclude with a summary of our accomplishments and make suggestions for some exciting future applications of our approach.

Localization of central sites of action of angiotensin II on ADH release in vitro

1978 ◽  
Vol 234 (2) ◽  
pp. F135-F140
Author(s):  
C. M. Gregg ◽  
R. L. Malvin
Keyword(s):  
Angiotensin Ii ◽  
Direct Action ◽  
Central Effect ◽  
The Central Nervous System ◽  
Sites Of Action ◽  
Isolated Rat ◽  
Supraoptic Nuclei ◽  
Stimulation Of

It is now thought that angiotensin II can stimulate antidiuretic hormone (ADH) release in vivo by a direct action in the central nervous system but it is not known whether the locus of stimulation is the hypothalamus or the neurohypophysis or both. Isolated rat neural lobes incubated for 10 min in buffer containing angiotensin II (200 ng/ml or 2 microgram/ml) did not increase ADH release compared to control values, but addition of KCl (60 mM) to the bath markedly stimulated ADH release. However, intact hypothalamoneurohypophysial systems (containing the supraoptic nuclei) incubated with angiotensin II (200 ng/ml or 2 microgram/ml) did show a pronounced stimulation of ADH release. The data support the hypothesis that angiotensin II, at least in vitro, has a central effect on ADH release which is at the level of the hypothalamus.

Myo-inositol transport in the central nervous system

1975 ◽  
Vol 228 (5) ◽  
pp. 1510-1518 ◽  
Author(s):  
R Spector ◽  
AV Lorenzo
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Choroid Plexus ◽  
Intraventricular Injection ◽  
Affinity Constant ◽  
Rapid Injection ◽  
The Central Nervous System

Free myo-inositol (inositol) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the cerebrospinal fluid was measured in rabbits. In vivo, inositol transport from blood into choroid plexus, CSF, and brain was saturable with an apparent affinity constant (K-t) of approximately 0.1 mM. The relative turnover of free inositol in choroid plexus (16 percent/h) was higher than in CSF 4percent/h) and brain (0.3percent/h) when meausred by tissue penetration of tracer [3-H]-labeled inositol injected into blood. However, the passage of tracer inositol was not greater than the passage of mannitol into brain when measured 15 s after a rapid injection of inositol and mannitol into the left common carotid artery. From the CSF, the clearance of inositol relative to inulin was saturable after the intraventricular injection of various concentrations of inositol and inulin. Moreover, a portion of the inositol cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [3-H-labeled myo-inositol against a concentration gradient by a specific, active, saturable process with a K-t of 0.2 mM inositol. These results were interpreted as showing that the entry of inositol into the central nervous system from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

scholarly journals Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine Compounds Compared to Dimethyl Fumarate

2020 ◽  
Vol 17 (3) ◽  
pp. 1142-1152 ◽  
Author(s):  
Karl E. Carlström ◽  
Praveen K. Chinthakindi ◽  
Belén Espinosa ◽  
Faiez Al Nimer ◽  
Elias S. J. Arnér ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
De Novo ◽  
Dimethyl Fumarate ◽  
The Novel ◽  
The Central Nervous System ◽  
Demyelinating Disorders ◽  
Target Effects

Abstract The Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone and sulfoximine compounds (CH-1–CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NFκB, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine CH-3 was the most promising candidate and selected for further comparison in vivo and later an experimental model for traumatic brain injury (TBI). CH-3 and DMF displayed comparable capacity to activate Nrf2 and downstream transcripts in vitro, but with less off-target effects on HIF1 from CH-3. This was verified in cultured microglia and oligodendrocytes (OLs) and subsequently in vivo in rats. Following TBI, DMF lowered the number of leukocytes in blood and also decreased axonal degeneration. CH-3 preserved or increased the number of pre-myelinating OL. While both CH-3 and DMF activated Nrf2, CH-3 showed less off-target effects and displayed more selective OL associated effects. Further studies with Nrf2-acting compounds are promising candidates to explore potential myelin protective or regenerative effects in demyelinating disorders.

scholarly journals In Vitro Analysis of Transneuronal Spread of an Alphaherpesvirus Infection in Peripheral Nervous System Neurons

2007 ◽  
Vol 81 (13) ◽  
pp. 6846-6857 ◽  
Author(s):  
B. Feierbach ◽  
M. Bisher ◽  
J. Goodhouse ◽  
L. W. Enquist
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Pseudorabies Virus ◽  
Viral Glycoprotein ◽  
In Vitro System ◽  
Vitro Analysis ◽  
In Vitro Analysis ◽  
Postsynaptic Target

ABSTRACT The neurotropic alphaherpesviruses invade and spread in the nervous system in a directional manner between synaptically connected neurons. Until now, this property has been studied only in living animals and has not been accessible to in vitro analysis. In this study, we describe an in vitro system in which cultured peripheral nervous system neurons are separated from their neuron targets by an isolator chamber ring. Using pseudorabies virus (PRV), an alphaherpesvirus capable of transneuronal spread in neural circuits of many animals, we have recapitulated in vitro all known genetic requirements for retrograde and anterograde transneuronal spread as determined previously in vivo. We show that in vitro transneuronal spread requires intact axons and the presence of the viral proteins gE, gI, and Us9. We also show that transneuronal spread is dependent on the viral glycoprotein gB, which is required for membrane fusion, but not on gD, which is required for extracellular spread. We demonstrate ultrastructural differences between anterograde- and retrograde-traveling virions. Finally, we show live imaging of dynamic fluorescent virion components in axons and postsynaptic target neurons.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

scholarly journals Functionalized Nanoparticles in Prevention and Targeted Therapy of Viral Diseases With Neurotropism Properties, Special Insight on COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Meishen Ren ◽  
Yin Wang ◽  
Yan Luo ◽  
Xueping Yao ◽  
Zexiao Yang ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Neutralizing Antibodies ◽  
Functionalized Nanoparticles ◽  
Neurotropic Viruses ◽  
The Central Nervous System ◽  
Recent Trends ◽  
Simplex Virus

Neurotropic viruses have neural-invasive and neurovirulent properties to damage the central nervous system (CNS), leading to humans’ fatal symptoms. Neurotropic viruses comprise a lot of viruses, such as Zika virus (ZIKV), herpes simplex virus (HSV), rabies virus (RABV), and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Effective therapy is needed to prevent infection by these viruses in vivo and in vitro. However, the blood-brain barrier (BBB) usually prevents macromolecules from entering the CNS, which challenges the usage of the traditional probes, antiviral drugs, or neutralizing antibodies in the CNS. Functionalized nanoparticles (NPs) have been increasingly reported in the targeted therapy of neurotropic viruses due to their sensitivity and targeting characteristics. Therefore, the present review outlines efficient functionalized NPs to further understand the recent trends, challenges, and prospects of these materials.

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