Abstract 68: Exosomes from Rhesus Monkey MSCs Promote Neuronal Growth and Myelination

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Benjamin Buller ◽  
Tara Moore ◽  
Yi Zhang ◽  
Elizabeth Pikula ◽  
Christopher Martin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Rhesus Monkey ◽  
Cortical Neurons ◽  
Therapeutic Potential ◽  
Brain Slices ◽  
Axonal Growth ◽  
Oligodendrocyte Progenitor Cells ◽  
Rat Pups ◽  
Functional Benefit ◽  
Microfluidic Chamber

Introduction: Treatment of rodents with bone marrow mesenchymal stromal cells (MSCs) enhances functional recovery after stroke. We have shown in a series of studies that much or all of this effect is mediated through release of exosomes--small, membrane bound vesicles that contain many biomolecules--by the MSCs, and that functional benefit is dependent on white matter remodeling. Hypothesis: We hypothesize that exosomes derived from monkey MSCs enhance axonal growth and myelination. Methods: We isolated MSCs from the bone marrow of a young adult rhesus monkey, and harvested their exosomes from MSC culture medium. Results: We first investigated the effect of exosomes on cultured organotypic brain slices from the cerebrum of rat pups. Treatment of brain slices with exosomes markedly increased myelination in cortex and corpus callosum compared to control. Image analysis of 3D reconstructions showed that exosomes increased connections of oligodendrocyte processes with axons by 48%, suggesting enhancement of initiation of myelination. To examine the effect of exosomes directly on neurons and oligodendrocyte progenitor cells (OPCs), exosomes were applied to either cortical neurons cultured in a microfluidic chamber or OPCs. We found that exosomes significantly (p<0.05) increased axonal length (526±22μm vs. 320±15μm for control, n=75/group) and increased the number of NG2+ OPCs by twofold compared to control (P < 0.01). However, exosomes had no significant effect on mature, MBP expressing oligodendrocytes. Conclusion: Our data suggest that exosomes enhance myelination by a two-pronged effect. First, they promote axonal growth, and second, they increase the number of available OPCs. Increased axonal growth may trigger OPCs to myelinate axons. This work is the first to demonstrate the therapeutic potential of monkey exosomes for axonal growth and myelination.

Structure–activity studies on the inhibition of γ-aminobutyric acid uptake in brain slices by compounds related to nipecotic acid

1979 ◽  
Vol 57 (6) ◽  
pp. 581-585 ◽  
Author(s):  
J. D. Wood ◽  
D. Tsui ◽  
J. W. Phillis
Keyword(s):  
Cortical Neurons ◽  
Therapeutic Potential ◽  
Brain Slices ◽  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Acid Uptake ◽  
Nipecotic Acid ◽  
Depressant Action ◽  
Methyl Derivatives ◽  
Derivatives Of

Various N-methyl derivatives of nipecotic acid and related compounds were tested as inhibitors of γ-aminobutyric acid (GABA) uptake into mini slices. N-Methylnipecotic acid, N,N-dimethyinipecotic acid, N-methylguvacine, and N-methylnicotinic acid were effective inhibitors. None of them, however, were as potent as nipecotic acid itself. All the effective inhibitors, including nipecotic acid, also inhibited the uptake of L-proline, but to a much lesser extent. Four of the test compounds produced a depressant action on cerebral cortical neurons, but even N-methylisoguvacine, the most potent in this respect, was considerably less active than GABA. None of the test compounds caused any clearly discernible changes in the gross behaviour or appearance of mice in the 1-h period following intramuscular injection. It was concluded that methylation of the N atom of nipecotic acid and its derivatives was unlikely to lead to the development of agents with greater experimental or therapeutic potential than that of nipecotic acid itself, if the action of the agent was dependent on its effects on GABA uptake.

scholarly journals Therapeutic potential of bone marrow-derived mesenchymal stem cells in formed aortic aneurysms of a mouse model

2014 ◽  
Vol 45 (5) ◽  
pp. e156-e165 ◽  
Author(s):  
A. Yamawaki-Ogata ◽  
X. Fu ◽  
R. Hashizume ◽  
K. L. Fujimoto ◽  
Y. Araki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Therapeutic Potential ◽  
Aortic Aneurysms

Abstract 3419: Positive Effect of Bone Marrow Progenitor Cell Transfer on Regional Post Infarction Ventricular Remodeling by Magnetic Resonance Imaging. Insights from the REPAIR AMI Trial.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Andreas Rolf ◽  
Susanne Mollmann ◽  
Johannes Rixe ◽  
Guido Conradi ◽  
Volker Schachinger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Placebo Group ◽  
Progenitor Cell ◽  
Ventricular Remodeling ◽  
Wall Thickening ◽  
Bone Marrow Progenitor Cell ◽  
Bone Marrow Progenitor ◽  
Functional Benefit ◽  
Adverse Remodeling ◽  
Positive Effect

Objective : The acute loss of myocytes during infarction increases loading conditions, which in turn triggers adverse remodeling of infarcted, adjacent and remote regions. Late Gadolinium Enhancement (LGE) cardiac MRI (CMR) can distinguish these regions and thus determine the effect of bone marrow progenitor cell (BMC) therapy on regional remodeling and function. Methods : 47 patients from the REPAIR AMI trial who underwent CMR at baseline and 12 month were evaluated in a segment by segment fashion according to the AHAs 17 segment model, defining LGE positive segments as infarcted and LGE negative segments as adjacent or remote. We measured enddiastolic wall diameters (WD) and wall thickening (WT) at 0 and 12 month by serial MRI. Results : WD decreased in all patients and all segments with a tendency to smaller diameters in BMC treated patients. In the prespecified subgroup of patients with larger infarcts (EF below the median of 48.9%) we observed a positive effect on adverse remodeling in BMC patients not only in infarcted but also in the remote areas. Infarcted segments showed a decrease in WD of 21.9% ± 4.0 SE in the BMC group vs. 8.5% ± 3.4 in the Placebo Group p=0.02. In BMC patients WD decreased in remote segments by 8.1% ± 4.4 SE compared to 4.9% ± 3.3 SE in the Placebo group, p=0.03. This effect on remodeling translates into a functional benefit. In remote segments WT decreases in both gropus but significantly so only in Placebo patients (BMC-7.8% ± 5.4 p= 0.2 vs. Placebo −13.9% ± 4.4 p=0.002, p for interaction 0.4). The largest effect was observed in the infarcted segments where BMC therapy led to an increase in WT of 26.6% ± 5.1 SE compared to Placebo 0.7% ± 4.6 SE p= 0.0001. The positive effect is mediated by wall diameters, regression analysis shows a significant inverse relationship between WD and WT, p = 0.0001 Conclusion : BMC therapy effectively prevents adverse remodeling not only in the infarct zone but also in remote segments for patients with large infarcts resulting in increased contractility. This seems to be mediated by a positive effect on enddiastolic wall geometry yielding smaller wall diameters.

scholarly journals Oxidative stress decreases pHi and Na+/H+ exchange and increases excitability of solitary complex neurons from rat brain slices

2004 ◽  
Vol 286 (4) ◽  
pp. C940-C951 ◽  
Author(s):  
Daniel K. Mulkey ◽  
Richard A. Henderson ◽  
Nick A. Ritucci ◽  
Robert W. Putnam ◽  
Jay B. Dean
Keyword(s):  
Oxidative Stress ◽  
Firing Rate ◽  
Brain Slices ◽  
Respiratory Control ◽  
Additive Effect ◽  
Rat Pups ◽  
Chloramine T ◽  
Fluorescence Imaging Microscopy ◽  
Solitary Complex ◽  
Whole Cell Recordings

Putative chemoreceptors in the solitary complex (SC) are sensitive to hypercapnia and oxidative stress. We tested the hypothesis that oxidative stress stimulates SC neurons by a mechanism independent of intracellular pH (pHi). pHi was measured by using ratiometric fluorescence imaging microscopy, utilizing either the pH-sensitive fluorescent dye BCECF or, during whole cell recordings, pyranine in SC neurons in brain stem slices from rat pups. Oxidative stress decreased pHi in 270 of 436 (62%) SC neurons tested. Chloramine-T (CT), N-chlorosuccinimide (NCS), dihydroxyfumaric acid, and H2O2 decreased pHi by 0.19 ± 0.007, 0.20 ± 0.015, 0.15 ± 0.013, and 0.08 ± 0.002 pH unit, respectively. Hypercapnia decreased pHi by 0.26 ± 0.006 pH unit ( n = 95). The combination of hypercapnia and CT or NCS had an additive effect on pHi, causing a 0.42 ± 0.03 ( n = 21) pH unit acidification. CT slowed pHi recovery mediated by Na+/H+ exchange (NHE) from NH4Cl-induced acidification by 53% ( n = 20) in [Formula: see text]-buffered medium and by 58% ( n = 10) in HEPES-buffered medium. CT increased firing rate in 14 of 16 SC neurons, and there was no difference in the firing rate response to CT with or without a corresponding change in pHi. These results indicate that oxidative stress 1) decreases pHi in some SC neurons, 2) together with hypercapnia has an additive effect on pHi, 3) partially inhibits NHE, and 4) directly affects excitability of CO2/H+-chemosensitive SC neurons independently of pHi changes. These findings suggest that oxidative stress acidifies SC neurons in part by inhibiting NHE, and this acidification may contribute ultimately to respiratory control dysfunction.

Sign in / Sign up

Export Citation Format

Share Document