scholarly journals An electroceutical approach enhances myelination via upregulation of lipid biosynthesis in the dorsal root ganglion

2021 ◽  
Author(s):  
Aseer Intisar ◽  
Woon-Hae Kim ◽  
Hyun Young Shin ◽  
Min Young Kim ◽  
Yu Seon Kim ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Muscular Atrophy ◽  
Ex Vivo ◽  
Lipid Biosynthesis ◽  
Foot Deformities ◽  
Ex Vivo Model ◽  
Myelin Lipids ◽  
Tof Sims ◽  
Biochemical Analyses

Abstract As the myelin sheath is crucial for neuronal saltatory conduction, loss of myelin in the peripheral nervous system (PNS) leads to demyelinating neuropathies causing muscular atrophy, numbness, foot deformities and paralysis. Unfortunately, few interventions are available for such neuropathies, because previous pharmaceuticals have shown severe side effects and failed in clinical trials. Therefore, exploring new strategies to enhance PNS myelination is critical to provide solution for such intractable diseases. This study aimed to investigate the effectiveness of electrical stimulation (ES) to enhance myelination in the mouse dorsal root ganglion (DRG) – an ex vivo model of the PNS. Mouse embryonic DRGs were extracted at E13 and seeded onto Matrigel-coated surfaces. After sufficient growth and differentiation, screening was carried out by applying ES in the 1-100 Hz range at the beginning of the myelination process. DRG myelination was evaluated via immunostaining at the intermediate (19 DIV) and mature (30 DIV) stages. Further biochemical analyses were carried out by utilizing RNA sequencing, qPCR and biochemical assays at both intermediate and mature myelination stages. Imaging of DRG myelin lipids was carried out via time-of-flight secondary ion mass spectrometry (ToF-SIMS). With screening ES conditions, optimal condition was identified at 20 Hz, which enhanced the percentage of myelinated neurons and average myelin length not only at intermediate (129% and 61%) but also at mature (72% and 17%) myelination stages. Further biochemical analyses elucidated that ES promoted lipid biosynthesis in the DRG. ToF-SIMS imaging showed higher abundance of the structural lipids, cholesterol and sphingomyelin, in the myelin membrane. Therefore, promotion of lipid biosynthesis and higher abundance of myelin lipids led to ES-mediated myelination enhancement. Given that myelin lipid deficiency is culpable for most demyelinating PNS neuropathies, the results might pave a new way to treat such diseases via electroceuticals.

scholarly journals Three-Dimensional Model of Dorsal Root Ganglion Explant as a Method of Studying Neurotrophic Factors in Regenerative Medicine

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 49 ◽  
Author(s):  
Polina Klimovich ◽  
Kseniya Rubina ◽  
Veronika Sysoeva ◽  
Ekaterina Semina
Keyword(s):  
Cell Migration ◽  
Green Fluorescent Protein ◽  
Dorsal Root Ganglion ◽  
Neurotrophic Factors ◽  
Dorsal Root ◽  
Fluorescent Protein ◽  
Axon Regeneration ◽  
Ex Vivo ◽  
Axon Growth ◽  
Green Fluorescent

Neurotrophic factors play a key role in the development, differentiation, and survival of neurons and nerve regeneration. In the present study, we evaluated the effect of certain neurotrophic factors (NGF, BDNF, and GDNF) on axon growth and migration of Nestin-green fluorescent protein (GFP)-positive cells using a 3D model of dorsal root ganglion (DRG) explant culture in Matrigel. Our method generally represents a convenient model for assessing the effects of soluble factors and therapeutic agents on axon growth and nerve regeneration in R&D studies. By analyzing the DRG explants in ex vivo culture for 21 days, one can evaluate the parameters of neurite outgrowth and the rate of cell migration from the DRG explants into the Matrigel. For the current study, we used Nestin-GFP-expressing mice in which neural precursors express Nestin and the green fluorescent protein (GFP) under the same promoter. We revealed that GDNF significantly (two fold) stimulated axon outgrowth (p < 0.05), but not BDNF or NGF. It is well-known that axon growth can be stimulated by activated glial cells that fulfill a trophic function for regenerating nerves. For this reason, we evaluated the number of Nestin-GFP-positive cells that migrated from the DRG into the Matrigel in our 3D ex vivo explant model. We found that NGF and GDNF, but not BDNF, stimulated the migration of Nestin-GFP cells compared to the control (p < 0.05). On the basis of the aforementioned finding, we concluded that GDNF had the greatest stimulating potential for axon regeneration, as it stimulated not only the axon outgrowth, but also glial cell migration. Although NGF significantly stimulated glial cell migration, its effect on axon growth was insufficient for axon regeneration.

1849: Systematic Evaluation of 21μm Thulium Laser Device for Treatment of Benign Prostatic Enlargement in an Ex-VIVO Model

2007 ◽  
Vol 177 (4S) ◽  
pp. 614-614 ◽  
Author(s):  
Gunnar Wendt-Nordahl ◽  
Stefanie Huckele ◽  
Patrick Honeck ◽  
Peter Aiken ◽  
Thomas Knoll ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Systematic Evaluation ◽  
Thulium Laser ◽  
Laser Device ◽  
Benign Prostatic Enlargement ◽  
Ex Vivo Model ◽  
Prostatic Enlargement

Porcine small intestine, a good ex vivo model to investigate absorption and metabolism of natural products

2017 ◽  
Author(s):  
J Houriet ◽  
YE Arnold ◽  
C Petit ◽  
YN Kalia ◽  
JL Wolfender
Keyword(s):  
Natural Products ◽  
Small Intestine ◽  
Ex Vivo ◽  
Ex Vivo Model

Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

1995 ◽  
Vol 73 (02) ◽  
pp. 219-222 ◽  
Author(s):  
Manuel Monreal ◽  
Luis Monreal ◽  
Rafael Ruiz de Gopegui ◽  
Yvonne Espada ◽  
Ana Maria Angles ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
In Vitro Study ◽  
Ex Vivo Model ◽  
Suitable Candidate ◽  
Significant Prolongation ◽  
High Doses ◽  
Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

EMR+: Vorstellung einer neuen endoskopischen Resektionsmethode im ex-vivo Model

2019 ◽  
Author(s):  
RF Knoop ◽  
E Wedi ◽  
V Ellenrieder ◽  
A Neesse ◽  
S Kunsch
Keyword(s):  
Ex Vivo ◽  
Ex Vivo Model
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