| Cell death and birth in multiple sclerosis brain. | |
| | |
MedLine Citation:
|
PMID: 9168159 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The hallmark of the brain pathology in multiple sclerosis is the white matter plaque, characterized by myelin destruction and oligodendrocyte loss. To examine the role that cell death plays in the development of MS lesions, we used the in situ TUNEL technique, a method that sensitively detects DNA fragmentation associated with death at the single cell level. We found that patchy areas within acute MS lesions have massive numbers of inflammatory and glial cells undergoing cell death. The punched out areas of some long-standing chronic lesions also had labeled glial cells showing that the attack was not a single event. Immunocytochemical identification of the dying cells with glial specific marker co-labeling showed that 14-40% were the myelin-sustaining oligodendroglial cell. Confocal microscopic evaluation of fluorescein-labeled TUNEL positive cells revealed nuclei with morphologic characteristics of apoptosis, and electrophoresed MS brain DNA produced a ladder characteristic of apoptotic DNA cleavage confirming that substantial numbers of labeled cells, but not necessarily all, were dying by apoptotic mechanisms rather than cell necrosis. Companion studies using a marker for cell proliferation on MS lesions revealed that unexpectedly large populations of perivascular inflammatory cells and parenchymal glial cells had entered the cell proliferation cycle. These findings establish that two opposing glial cell responses - relentless cell death and coincident brisk cellular proliferation - are important features of MS pathology. In the end, however, glial cell loss prevails, and we suspect apoptosis may be the critical death mechanism responsible for the depletion of myelin observed in this condition. |
| | |
Authors:
|
P Dowling; W Husar; J Menonna; H Donnenfeld; S Cook; M Sidhu |
Related Documents
:
|
16870259 - Proteasome inhibitor mg-132 induces dopaminergic degeneration in cell culture and anima... 17200679 - Stroke induces ependymal cell transformation into radial glia in the subventricular zon... 12966219 - The cortical ancestry of oligodendrocytes: common principles and novel features. 12510019 - Effect of reactive cell density on net [2-14c]acetate uptake into rat brain: labeling o... 2580799 - A dual expression of cytokeratin and neurofilaments in bronchial carcinoid cells. 9010219 - Nuclear accumulation of fgf-2 is associated with proliferation of human astrocytes and ... 15383319 - Cholesterol is essential for mitosis progression and its deficiency induces polyploid c... 1057159 - Nucleotide composition analysis of trna from leukemia patient cell samples and human ce... 20512979 - Glycoprotein production for structure analysis with stable, glycosylation mutant cho ce... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: Journal of the neurological sciences Volume: 149 ISSN: 0022-510X ISO Abbreviation: J. Neurol. Sci. Publication Date: 1997 Jul |
Date Detail:
|
Created Date: 1997-07-10 Completed Date: 1997-07-10 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0375403 Medline TA: J Neurol Sci Country: NETHERLANDS |
Other Details:
|
Languages: eng Pagination: 1-11 Citation Subset: IM |
Affiliation:
|
Department of Veterans Affairs, New Jersey Health Care System, East Orange 07018, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis* Autopsy Biological Markers Brain / pathology* Cell Nucleus / pathology, ultrastructure Central Nervous System Diseases / pathology Child DNA Fragmentation Encephalomyelitis, Autoimmune, Experimental / pathology Glial Fibrillary Acidic Protein / analysis Humans Immunoenzyme Techniques Ki-67 Antigen / analysis Multiple Sclerosis / pathology* Myelin Sheath / pathology, ultrastructure Neuroglia / pathology Neurons / pathology* Oligodendroglia / pathology, ultrastructure Rats Rats, Inbred Lew Sensitivity and Specificity Spinal Cord / pathology* |
| Chemical | |
Reg. No./Substance:
|
0/Biological Markers; 0/Glial Fibrillary Acidic Protein; 0/Ki-67 Antigen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: In vitro study of passive nitrate transport by native and reconstituted plasma membrane vesicles fro...
Next Document: Delayed neurite regeneration and its improvement by nerve growth factor (NGF) in dorsal root ganglia...