Document Detail


Triptans reduce the inflammatory response in bacterial meningitis.
MedLine Citation:
PMID:  12172384     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Severe headache and meningism provide clear evidence for the activation of trigeminal neurotransmission in meningitis. The authors assessed the antiinflammatory potential of 5HT1B/D/F receptor agonists (triptans), which inhibit the release of proinflammatory neuropeptides from perivascular nerve fibers. In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow. Elevated intracranial pressure as well as the brain water content at 6 hours was reduced by triptans. These effects were partially reversed by a specific 5HT1D as well as by a specific 5HT1B receptor antagonist. Meningitis caused a depletion of calcitonin gene-related peptide (CGRP) and substance P from meningeal nerve fibers, which was prevented by zolmitriptan and naratriptan. In line with these findings, patients with bacterial meningitis had significantly elevated CGRP levels in the cerebrospinal fluid. In a mouse model of pneumococcal meningitis, survival and clinical score at 24 hours were significantly improved by triptan treatment. The findings suggest that, besides mediating meningeal nociception, meningeal nerve fibers contribute to the inflammatory cascade in the early phase of bacterial meningitis. Adjunctive treatment with triptans may open a new therapeutic approach in the acute phase of bacterial meningitis.
Authors:
Olaf Hoffmann; Nikolas Keilwerth; Margarethe Bastholm Bille; Uwe Reuter; Klemens Angstwurm; Ralf R Schumann; Ulrich Dirnagl; Joerg R Weber
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  22     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-12     Completed Date:  2002-09-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  988-96     Citation Subset:  IM    
Affiliation:
Department of Neurology, University Hospital Charité, Humboldt University, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology,  therapeutic use*
Benzamides / pharmacology
Calcitonin Gene-Related Peptide / cerebrospinal fluid,  metabolism
Cerebrovascular Circulation / drug effects
Dura Mater / cytology,  metabolism
Humans
Indoles / pharmacology,  therapeutic use*
Laser-Doppler Flowmetry
Leukocytes / immunology,  metabolism
Male
Meningitis, Pneumococcal / drug therapy*,  physiopathology
Mice
Mice, Inbred Strains
Oxadiazoles / pharmacology
Oxazolidinones / pharmacology,  therapeutic use*
Piperidines / pharmacology,  therapeutic use*
Rats
Rats, Wistar
Receptor, Serotonin, 5-HT1B
Receptors, Serotonin / metabolism
Serotonin Agonists / pharmacology,  therapeutic use*
Serotonin Antagonists / pharmacology
Substance P / metabolism
Survival Rate
Tryptamines
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Benzamides; 0/HTR1B protein, human; 0/Indoles; 0/N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; 0/Oxadiazoles; 0/Oxazolidinones; 0/Piperidines; 0/Receptor, Serotonin, 5-HT1B; 0/Receptors, Serotonin; 0/Serotonin Agonists; 0/Serotonin Antagonists; 0/Tryptamines; 121679-13-8/naratriptan; 139264-17-8/zolmitriptan; 33507-63-0/Substance P; 83652-28-2/Calcitonin Gene-Related Peptide

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