scholarly journals In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice.

1989 ◽  
Vol 109 (5) ◽  
pp. 2405-2416 ◽  
Author(s):  
C Godfraind ◽  
V L Friedrich ◽  
K V Holmes ◽  
M Dubois-Dalcq
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Glial Cell ◽  
Demyelinating Disease ◽  
Tritiated Thymidine ◽  
Disease Process ◽  
Demyelinating Lesions ◽  
Immunofluorescence Labeling

C57 BL/6N mice injected intracranially with the A59 strain of mouse hepatitis virus exhibit extensive viral replication in glial cells of the spinal cord and develop demyelinating lesions followed by virus clearing and remyelination. To study how different glial cell types are affected by the disease process, we combine three-color immunofluorescence labeling with tritiated thymidine autoradiography on 1-micron frozen sections of spinal cord. We use three different glial cell specific antibodies (a) to 2',3' cyclic-nucleotide 3' phosphohydrolase (CNP) expressed by oligodendrocytes, (b) to glial fibrillary acidic protein (GFAP) expressed by astrocytes, and (c) the O4 antibody which binds to O-2A progenitor cells in the rat. These progenitor cells, which give rise to oligodendrocytes and type 2 astrocytes and react with the O4 antibody in the adult central nervous system, were present but rare in the spinal cord of uninfected mice. In contrast, cells with the O-2A progenitor phenotype (O4 + only) were increased in number at one week post viral inoculation (1 WPI) and were the only immunostained cells labeled at that time by a 2-h in vivo pulse of tritiated thymidine. Both GFAP+ only and GFAP+, O4+ astrocytes were also increased in the spinal cord at 1 WPI. Between two and four WPI, the infected spinal cord was characterized by the loss of (CNP+, O4+) oligodendrocytes within demyelinating lesions and the presence of O-2A progenitor cells and O4+, GFAP+ astrocytes, both of which could be labeled with thymidine. As remyelination proceeded, CNP immunostaining returned to near normal and tritiated thymidine injected previously during the demyelinating phase now appeared in CNP+ oligodendrocytes. Thus O4 positive O-2A progenitor cells proliferate early in the course of the demyelinating disease, while CNP positive oligodendrocytes do not. The timing of events suggests that the O-2A progenitors may give rise to new oligodendrocytes and to type 2 astrocytes, both of which are likely to be instrumental in the remyelination process.

Transplantation of Neural Stem/Progenitor Cells at Different Locations in Mice with Spinal Cord Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1451-1464 ◽  
Author(s):  
Hiroki Iwai ◽  
Satoshi Nori ◽  
Soraya Nishimura ◽  
Akimasa Yasuda ◽  
Morito Takano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Functional Recovery ◽  
Control Group ◽  
Cord Injury ◽  
Neural Stem Progenitor Cells ◽  
Neurotropic Factor ◽  
Transplantation Site

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

scholarly journals Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus

Circulation ◽  
2007 ◽  
Vol 116 (2) ◽  
pp. 163-173 ◽  
Author(s):  
Sajoscha A. Sorrentino ◽  
Ferdinand H. Bahlmann ◽  
Christian Besler ◽  
Maja Müller ◽  
Svenja Schulz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Oxidant Stress ◽  
Endothelial Progenitor

Serotonergic manipulations in experimental neoplastic spinal cord compression

1993 ◽  
Vol 78 (6) ◽  
pp. 929-937 ◽  
Author(s):  
Tali Siegal ◽  
Tzony Siegal
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Clinical Course ◽  
Fold Increase ◽  
Cord Compression ◽  
Neurological Dysfunction ◽  
Prostaglandin E ◽  
Content Type

✓ The effects of differing strategies of serotonergic manipulation on vascular permeability, prostaglandin E2 (PGE2) synthesis, and the clinical course are evaluated in an experimental model of neoplastic spinal cord compression in rats. Serotonergic manipulations include in vivo inhibition of serotonin (5-HT) synthesis by p-chlorophenylalanine (p-CPA) and in vivo blockage of serotonin type 2 (5-HT2) receptors either by the selective antagonist ketanserin or by cyproheptadine. In paralyzed rats, the ratio of 5-hydroxyindole-3-acetic acid (5-HIAA) to 5-HT is significantly elevated in the compressed segments, suggesting that 5-HT utilization is increased. Treatment with p-CPA attenuates spinal 5-HT levels by 62.8% ± 5.1% (mean ± standard deviation) and reduces the elevated 5-HIAA:5-HT ratio to the normal value. The increased synthesis of PGE2 observed in the compressed cord is unaffected by p-CPA or ketanserin treatment but is markedly attenuated by cyproheptadine. Ketanserin reduces the 10-fold increase in spinal cord permeability observed in paralyzed rats in a clearly dose-related manner. If given at the first sign of neurological dysfunction, ketanserin delays the onset of paraplegia with the 1-mg/kg dose being clearly superior. Cyproheptadine and p-CPA also reduce the increased permeability and protract the course to paraplegia. A comparison of the effect of dexamethasone, indomethacin, cyproheptadine, p-CPA, and ketanserin reveals that they protract the disease course by 48%, 57%, 60%, 64%, and 78%, respectively. These data suggest that 5-HT2 receptors mediate some of the deleterious vascular consequences observed in the compressed spinal cord by a mechanism not coupled with PGE2 synthesis. A potential benefit of serotonergic manipulations for the acute treatment of neoplastic spinal cord compression is suggested.

scholarly journals Axonal Damage in Multiple Sclerosis Patients with High versus Low Expanded Disability Status Scale Score

2004 ◽  
Vol 31 (2) ◽  
pp. 225-228 ◽  
Author(s):  
Steven D. Brass ◽  
Sridar Narayanan ◽  
Jack P. Antel ◽  
Yves Lapierre ◽  
Louis Collins ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Disease Process ◽  
Resonance Spectroscopy ◽  
Lesion Volume ◽  
Spinal Cord Atrophy ◽  
Neuronal Marker ◽  
Multiple Sclerosis Patients

AbstractBackground:The pathophysiological basis for differences in disability in patients with multiple sclerosis is unclear.Methods:We used magnetic resonance imaging to examine whether differences in disability in cohorts of multiple sclerosis patients with similar T2-weighted lesion volume and disease duration were associated with a more destructive disease process in the more disabled patients.Results:The benign and severely disabled groups had similar brain atrophy metrics and similar decreases of the neuronal marker, N-acetylaspartate, in the normal appearing white matter of the cerebrum on magnetic resonance spectroscopy examination in vivo. The severely disabled cohort had more spinal cord atrophy.Conclusion:The dissociation of spinal cord atrophy and cerebral atrophy between these two groups suggests that the difference between the more benign and more disabled groups cannot be explained by a more aggressive pathological process that is affecting the entire neuroaxis in a homogeneous fashion.

scholarly journals A Novel Lysolecithin Model for Visualizing Damage in vivo in the Larval Zebrafish Spinal Cord

2021 ◽  
Vol 9 ◽  
Author(s):  
Angela D. Morris ◽  
Sarah Kucenas
Keyword(s):  
Spinal Cord ◽  
Temporal Dynamics ◽  
Cell Loss ◽  
Time Lapse ◽  
Clinical Patient ◽  
Injection Model ◽  
Demyelinating Lesions ◽  
Therapeutic Compounds ◽  
Time Lapse Imaging

Background: Lysolecithin is commonly used to induce demyelinating lesions in the spinal cord and corpus callosum of mammalian models. Although these models and clinical patient samples are used to study neurodegenerative diseases, such as multiple sclerosis (MS), they do not allow for direct visualization of disease-related damage in vivo. To overcome this limitation, we created and characterized a focal lysolecithin injection model in zebrafish that allows us to investigate the temporal dynamics underlying lysolecithin-induced damage in vivo.Results: We injected lysolecithin into 4–6 days post-fertilization (dpf) zebrafish larval spinal cords and, coupled with in vivo, time-lapse imaging, observed hallmarks consistent with mammalian models of lysolecithin-induced demyelination, including myelinating glial cell loss, myelin perturbations, axonal sparing, and debris clearance.Conclusion: We have developed and characterized a lysolecithin injection model in zebrafish that allows us to investigate myelin damage in a living, vertebrate organism. This model may be a useful pre-clinical screening tool for investigating the safety and efficacy of novel therapeutic compounds that reduce damage and/or promote repair in neurodegenerative disorders, such as MS.

scholarly journals Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Darpan Saraswat ◽  
Hani J. Shayya ◽  
Jessie J. Polanco ◽  
Ajai Tripathi ◽  
R. Ross Welliver ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progenitor Cells ◽  
Demyelinating Disease ◽  
Heparan Sulfate Proteoglycans ◽  
Oligodendrocyte Progenitor Cells ◽  
Subsequent Generation ◽  
Oligodendrocyte Progenitor ◽  
Demyelinating Lesions ◽  
Experimental Demyelination

AbstractChronic demyelination in the human CNS is characterized by an inhibitory microenvironment that impairs recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) leading to failed remyelination and axonal atrophy. By network-based transcriptomics, we identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans. We found that Sulf2 was increased in demyelinating lesions in multiple sclerosis and was actively secreted by human OPCs. In experimental demyelination, elevated OPC Sulf1/2 expression directly impaired progenitor recruitment and subsequent generation of oligodendrocytes thereby limiting remyelination. Sulf1/2 potentiates the inhibitory microenvironment by promoting BMP and WNT signaling in OPCs. Importantly, pharmacological sulfatase inhibition using PI-88 accelerated oligodendrocyte recruitment and remyelination by blocking OPC-expressed sulfatases. Our findings define an important inhibitory role of Sulf1/2 and highlight the potential for modulation of the heparanome in the treatment of chronic demyelinating disease.

Sign in / Sign up

Export Citation Format

Share Document