| Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion. | |
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MedLine Citation:
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PMID: 14725965 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We examined the expression of TNF-alpha within the substantia nigra pars reticulata (SNR) following intrastriatal injection of quinolinic acid (QA) and studied the effect of rolipram, a TNF-alpha-inhibitor, on the secondary neuronal damage. QA (240 nmol in 1 microl) was injected stereotactically into the striatum of male Wistar rats. After survival of 1, 3 or 10 days, the animals were sacrificed and immunohistochemical staining with an antibody against TNF-alpha was performed. From day 1 to day 10 after striatal QA injection TNF-alpha positive cells were observed within ipsilateral substantia nigra which were neither present on the contralateral side nor in sham-operated controls. Double labeling with antibodies against TNF-alpha and NeuN, keratan sulfate proteoglycan or GFAP displayed a good overlap between TNF-alpha and NeuN, which suggests that TNF-alpha positive cells are neurons. For the pharmacological approach, three groups of QA rats were treated intraperitoneally with either solvent (n=5), the NMDA receptor antagonist MK 801 (4 mg/kg, n=6) or the TNF-alpha inhibitor rolipram (0.3 mg/kg, n=6), which was started 24 h after QA-injection and continued with daily applications for 14 days. The amount of striatal damage did not differ between the three groups. The number of intact neurons within the ipsilateral substantia nigra of the solvent treated group was reduced by approximately 30% compared to the contralateral side. Both MK 801 and rolipram ameliorated this secondary damage and reduced the number of TNF-alpha positive cells. The observed association between expression of TNF-alpha and secondary neuronal damage within the substantia nigra induced by intrastriatal QA application might hint towards an involvement of this cytokine in transneuronal degeneration. |
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Authors:
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F Block; M Loos; C Frohn; M Schwarz |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Brain research Volume: 998 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2004-01-16 Completed Date: 2004-03-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 29-35 Citation Subset: IM |
Affiliation:
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Department of Neurology, University of Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany. fblock@ukaachen.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Diseases / metabolism, physiopathology* Cell Count Corpus Striatum / injuries, physiopathology* Dizocilpine Maleate / pharmacology Excitatory Amino Acid Antagonists / pharmacology Functional Laterality Glial Fibrillary Acidic Protein / metabolism Immunohistochemistry / methods Inflammation / chemically induced, etiology, metabolism Keratan Sulfate / metabolism Male Phosphodiesterase Inhibitors / pharmacology Phosphopyruvate Hydratase / metabolism Proteochondroitin Sulfates / metabolism Quinolinic Acid / toxicity Rats Rats, Wistar Rolipram / pharmacology Substantia Nigra / drug effects, metabolism, physiopathology* Time Factors Tumor Necrosis Factor-alpha / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Excitatory Amino Acid Antagonists; 0/Glial Fibrillary Acidic Protein; 0/Phosphodiesterase Inhibitors; 0/Proteochondroitin Sulfates; 0/Tumor Necrosis Factor-alpha; 0/lumican; 61413-54-5/Rolipram; 77086-22-7/Dizocilpine Maleate; 89-00-9/Quinolinic Acid; 9056-36-4/Keratan Sulfate; EC 4.2.1.11/Phosphopyruvate Hydratase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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