| Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis. | |
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MedLine Citation:
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PMID: 12677451 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bacterial meningitis causes neuronal apoptosis in the hippocampal dentate gyrus, which is associated with learning and memory impairments after cured disease. The execution of the apoptotic program involves pathways that converge on activation of caspase-3, which is required for morphological changes associated with apoptosis. Here, the time course and the role of caspase-3 in neuronal apoptosis was assessed in an infant rat model of pneumococcal meningitis. During clinically asymptotic meningitis (0-12 h after infection), only minor apoptotic damage to the dentate gyrus was observed, while the acute phase (18-24 h) was characterized by a massive increase of apoptotic cells, which peaked at 36 h. In the subacute phase of the disease (36-72 h), the number of apoptotic cells decreased to control levels. Enzymatic caspase-3 activity was significantly increased in hippocampal tissue of infected animals compared to controls at 22 h. The activated enzyme was localized to immature cells of the dentate gyrus, and in vivo activity was evidenced by cleavage of the amyloid-beta precursor protein. Intracisternal administration of the caspase-3-specific inhibitor Ac-DEVD-CHO significantly reduced apoptosis in the hippocampal dentate gyrus. In contrast to a study where the decrease of hippocampal apoptosis after administration of a pan-caspase inhibitor was due to downmodulation of the inflammatory response, our data demonstrate that specific inhibition of caspase-3 did not affect inflammation assessed by TNF-alpha and IL-1beta concentrations in the cerebrospinal fluid space. Taken together, the present results identify caspase-3 as a key effector of neuronal apoptosis in pneumococcal meningitis. |
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Authors:
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Christian Gianinazzi; Denis Grandgirard; Hans Imboden; Lotti Egger; Damian N Meli; Yoeng-Delphine Bifrare; Philipp C Joss; Martin G Täuber; Christoph Borner; Stephen L Leib |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2003-02-12 |
Journal Detail:
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Title: Acta neuropathologica Volume: 105 ISSN: 0001-6322 ISO Abbreviation: Acta Neuropathol. Publication Date: 2003 May |
Date Detail:
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Created Date: 2003-04-04 Completed Date: 2003-06-06 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0412041 Medline TA: Acta Neuropathol Country: Germany |
Other Details:
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Languages: eng Pagination: 499-507 Citation Subset: IM |
Affiliation:
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Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, 3010 Bern, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid beta-Protein
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metabolism Animals Apoptosis* Blotting, Western Body Weight Caspase 3 Caspases / physiology* Cerebral Cortex / metabolism Coumarins / administration & dosage Cysteine Proteinase Inhibitors / administration & dosage DNA Fragmentation Disease Models, Animal Hippocampus / enzymology, pathology* Humans Immunohistochemistry In Situ Nick-End Labeling / methods Interleukin-1 Meningitis, Pneumococcal / enzymology, metabolism, pathology* Nerve Tissue Proteins / metabolism Neurons / physiology Nuclear Proteins / metabolism Oligopeptides / administration & dosage Pneumococcal Infections Rats Rats, Sprague-Dawley Time Factors Tumor Necrosis Factor-alpha / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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NS-35902/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ac-aspartyl-glutamyl-valyl-aspartyl-aminomethylcoumarin; 0/Amyloid beta-Protein; 0/Coumarins; 0/Cysteine Proteinase Inhibitors; 0/Interleukin-1; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Oligopeptides; 0/Tumor Necrosis Factor-alpha; 0/neugrin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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