Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis
Neuronal injury is frequent in bacterial meningitis, resulting in a high rate of death and neurological sequelae. In a search of potential neuroprotective strategies for treatment of bacterial meningitis, the antioxidant melatonin was neuroprotective in cell culture experiments and in a rabbit Strep...
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| Veröffentlicht in: | Journal of neuroscience research 2006-11, Vol.84 (7), p.1575-1579 |
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| container_title | Journal of neuroscience research |
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| creator | Spreer, Annette Gerber, Joachim Baake, Daniel Hanssen, Mareike Huether, Gerald Nau, Roland |
| description | Neuronal injury is frequent in bacterial meningitis, resulting in a high rate of death and neurological sequelae. In a search of potential neuroprotective strategies for treatment of bacterial meningitis, the antioxidant melatonin was neuroprotective in cell culture experiments and in a rabbit Streptococcus pneumoniae meningitis model, when treatment was started at the time of infection. In the present study, adjunctive melatonin treatment applied from the beginning of antibiotic therapy 12 hr after infection at a dose of 1.67 mg/kg/hr resulted in plasma concentrations of 451 ± 198 ng/ml, cerebrospinal fluid (CSF) concentrations of 154 ± 57 ng/ml and a CSF‐to‐plasma ratio of 0.38 ± 0.19 (mean ± SD). Melatonin therapy had antiinflammatory effects but did not reduce neuronal injury in either a rabbit model of gram‐positive Streptococcus pneumoniae or gram‐negative Escherichia coli meningitis. © 2006 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jnr.21055 |
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In a search of potential neuroprotective strategies for treatment of bacterial meningitis, the antioxidant melatonin was neuroprotective in cell culture experiments and in a rabbit Streptococcus pneumoniae meningitis model, when treatment was started at the time of infection. In the present study, adjunctive melatonin treatment applied from the beginning of antibiotic therapy 12 hr after infection at a dose of 1.67 mg/kg/hr resulted in plasma concentrations of 451 ± 198 ng/ml, cerebrospinal fluid (CSF) concentrations of 154 ± 57 ng/ml and a CSF‐to‐plasma ratio of 0.38 ± 0.19 (mean ± SD). Melatonin therapy had antiinflammatory effects but did not reduce neuronal injury in either a rabbit model of gram‐positive Streptococcus pneumoniae or gram‐negative Escherichia coli meningitis. © 2006 Wiley‐Liss, Inc.</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.21055</identifier><identifier>PMID: 16998917</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Anti-Inflammatory Agents - therapeutic use ; Antioxidants - therapeutic use ; Apoptosis - drug effects ; bacterial meningitis ; Cell Count - methods ; Dinoprostone - cerebrospinal fluid ; Disease Models, Animal ; Escherichia coli ; hippocampal dentate gyrus ; Hippocampus - microbiology ; Hippocampus - pathology ; Melatonin - therapeutic use ; melatonin pharmacokinetics ; Meningitis, Bacterial - cerebrospinal fluid ; Meningitis, Bacterial - complications ; Meningitis, Bacterial - drug therapy ; neuronal apoptosis ; Neurons - drug effects ; Rabbits ; Statistics, Nonparametric ; Streptococcus pneumoniae ; Time Factors</subject><ispartof>Journal of neuroscience research, 2006-11, Vol.84 (7), p.1575-1579</ispartof><rights>Copyright © 2006 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3615-eacfe6791b8b8cd9a045e8051f8af0312aabf15c2c7841f34cbcd38325ab4dec3</citedby><cites>FETCH-LOGICAL-c3615-eacfe6791b8b8cd9a045e8051f8af0312aabf15c2c7841f34cbcd38325ab4dec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.21055$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.21055$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16998917$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spreer, Annette</creatorcontrib><creatorcontrib>Gerber, Joachim</creatorcontrib><creatorcontrib>Baake, Daniel</creatorcontrib><creatorcontrib>Hanssen, Mareike</creatorcontrib><creatorcontrib>Huether, Gerald</creatorcontrib><creatorcontrib>Nau, Roland</creatorcontrib><title>Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis</title><title>Journal of neuroscience research</title><addtitle>J. Neurosci. Res</addtitle><description>Neuronal injury is frequent in bacterial meningitis, resulting in a high rate of death and neurological sequelae. In a search of potential neuroprotective strategies for treatment of bacterial meningitis, the antioxidant melatonin was neuroprotective in cell culture experiments and in a rabbit Streptococcus pneumoniae meningitis model, when treatment was started at the time of infection. In the present study, adjunctive melatonin treatment applied from the beginning of antibiotic therapy 12 hr after infection at a dose of 1.67 mg/kg/hr resulted in plasma concentrations of 451 ± 198 ng/ml, cerebrospinal fluid (CSF) concentrations of 154 ± 57 ng/ml and a CSF‐to‐plasma ratio of 0.38 ± 0.19 (mean ± SD). Melatonin therapy had antiinflammatory effects but did not reduce neuronal injury in either a rabbit model of gram‐positive Streptococcus pneumoniae or gram‐negative Escherichia coli meningitis. © 2006 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Antioxidants - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>bacterial meningitis</subject><subject>Cell Count - methods</subject><subject>Dinoprostone - cerebrospinal fluid</subject><subject>Disease Models, Animal</subject><subject>Escherichia coli</subject><subject>hippocampal dentate gyrus</subject><subject>Hippocampus - microbiology</subject><subject>Hippocampus - pathology</subject><subject>Melatonin - therapeutic use</subject><subject>melatonin pharmacokinetics</subject><subject>Meningitis, Bacterial - cerebrospinal fluid</subject><subject>Meningitis, Bacterial - complications</subject><subject>Meningitis, Bacterial - drug therapy</subject><subject>neuronal apoptosis</subject><subject>Neurons - drug effects</subject><subject>Rabbits</subject><subject>Statistics, Nonparametric</subject><subject>Streptococcus pneumoniae</subject><subject>Time Factors</subject><issn>0360-4012</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10MFuFSEYBWBibOy1uvAFDCsTF9PCMAzDsrnRVtNcG6PRuCHA_BjqDFRgtPcRfGtp79WuuuJffOckHIReUHJMCWlPrkI6binh_BFaUSJF0_FOPEYrwnrSdIS2h-hpzleEECk5e4IOaS_lIKlYoT-noXgf3KTnWZeYttgsBYeIAywpXqdYwBb_CzA4V6-Mo8MzTJUGH_ASRkjYTj54qydcEugyQyjYxjD64mPIuLKkjfEFz3GE6a7BaFsg-Rqp2ofvleZn6MDpKcPz_XuEPr9982l93lx8OHu3Pr1oLOspb0BbB72Q1AxmsKPUpOMwEE7doB1htNXaOMpta8XQUcc6a-zIBtZybboRLDtCr3a99XM_F8hFzT5bmCYdIC5Z9YMUsme8wtc7aFPMOYFT18nPOm0VJep2d1V3V3e7V_tyX7qYGcZ7uR-6gpMd-O0n2D7cpN5vPv6rbHYJnwvc_E_o9EP1ggmuvmzO1Ldus-4vL4X6yv4C_-egxw</recordid><startdate>20061115</startdate><enddate>20061115</enddate><creator>Spreer, Annette</creator><creator>Gerber, Joachim</creator><creator>Baake, Daniel</creator><creator>Hanssen, Mareike</creator><creator>Huether, Gerald</creator><creator>Nau, Roland</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20061115</creationdate><title>Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis</title><author>Spreer, Annette ; Gerber, Joachim ; Baake, Daniel ; Hanssen, Mareike ; Huether, Gerald ; Nau, Roland</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3615-eacfe6791b8b8cd9a045e8051f8af0312aabf15c2c7841f34cbcd38325ab4dec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Antioxidants - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>bacterial meningitis</topic><topic>Cell Count - methods</topic><topic>Dinoprostone - cerebrospinal fluid</topic><topic>Disease Models, Animal</topic><topic>Escherichia coli</topic><topic>hippocampal dentate gyrus</topic><topic>Hippocampus - microbiology</topic><topic>Hippocampus - pathology</topic><topic>Melatonin - therapeutic use</topic><topic>melatonin pharmacokinetics</topic><topic>Meningitis, Bacterial - cerebrospinal fluid</topic><topic>Meningitis, Bacterial - complications</topic><topic>Meningitis, Bacterial - drug therapy</topic><topic>neuronal apoptosis</topic><topic>Neurons - drug effects</topic><topic>Rabbits</topic><topic>Statistics, Nonparametric</topic><topic>Streptococcus pneumoniae</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spreer, Annette</creatorcontrib><creatorcontrib>Gerber, Joachim</creatorcontrib><creatorcontrib>Baake, Daniel</creatorcontrib><creatorcontrib>Hanssen, Mareike</creatorcontrib><creatorcontrib>Huether, Gerald</creatorcontrib><creatorcontrib>Nau, Roland</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spreer, Annette</au><au>Gerber, Joachim</au><au>Baake, Daniel</au><au>Hanssen, Mareike</au><au>Huether, Gerald</au><au>Nau, Roland</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis</atitle><jtitle>Journal of neuroscience research</jtitle><addtitle>J. Neurosci. Res</addtitle><date>2006-11-15</date><risdate>2006</risdate><volume>84</volume><issue>7</issue><spage>1575</spage><epage>1579</epage><pages>1575-1579</pages><issn>0360-4012</issn><eissn>1097-4547</eissn><abstract>Neuronal injury is frequent in bacterial meningitis, resulting in a high rate of death and neurological sequelae. In a search of potential neuroprotective strategies for treatment of bacterial meningitis, the antioxidant melatonin was neuroprotective in cell culture experiments and in a rabbit Streptococcus pneumoniae meningitis model, when treatment was started at the time of infection. In the present study, adjunctive melatonin treatment applied from the beginning of antibiotic therapy 12 hr after infection at a dose of 1.67 mg/kg/hr resulted in plasma concentrations of 451 ± 198 ng/ml, cerebrospinal fluid (CSF) concentrations of 154 ± 57 ng/ml and a CSF‐to‐plasma ratio of 0.38 ± 0.19 (mean ± SD). Melatonin therapy had antiinflammatory effects but did not reduce neuronal injury in either a rabbit model of gram‐positive Streptococcus pneumoniae or gram‐negative Escherichia coli meningitis. © 2006 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>16998917</pmid><doi>10.1002/jnr.21055</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - therapeutic use Antioxidants - therapeutic use Apoptosis - drug effects bacterial meningitis Cell Count - methods Dinoprostone - cerebrospinal fluid Disease Models, Animal Escherichia coli hippocampal dentate gyrus Hippocampus - microbiology Hippocampus - pathology Melatonin - therapeutic use melatonin pharmacokinetics Meningitis, Bacterial - cerebrospinal fluid Meningitis, Bacterial - complications Meningitis, Bacterial - drug therapy neuronal apoptosis Neurons - drug effects Rabbits Statistics, Nonparametric Streptococcus pneumoniae Time Factors |
| title | Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis |
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