Altered inflammatory responses in preterm children with cerebral palsy
Objective Perinatal inflammatory responses contribute to periventricular leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined whether preterm children with CP had altered inflammatory responses when school‐aged. Methods Thirty‐two preterm children with PVL‐induced CP (mea...
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| Veröffentlicht in: | Annals of neurology 2010-08, Vol.68 (2), p.204-212 |
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| creator | Lin, Chang-Yi Chang, Ying-Chao Wang, Shan-Tair Lee, Ting-Yang Lin, Chiou-Feng Huang, Chao-Ching |
| description | Objective
Perinatal inflammatory responses contribute to periventricular leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined whether preterm children with CP had altered inflammatory responses when school‐aged.
Methods
Thirty‐two preterm children with PVL‐induced CP (mean [±standard deviation] age, 7.2 ± 3.6 years) and 32 control preterm children with normal neurodevelopment (6.2 ± 2.2 years) and matched for gestational age were recruited. We measured tumor necrosis factor (TNF)‐α levels in the plasma and the supernatants of peripheral blood mononuclear cells (PBMCs) before and after lipopolysaccharide (LPS) stimulation, and proinflammatory gene expression in the PBMCs.
Results
TNF‐α expression was significantly higher in the plasma (p < 0.001) and supernatants of LPS‐stimulated PBMCs (p = 0.003) in the CP group than in the control group. After LPS stimulation, the intracellular TNF‐α level in the PBMCs was significantly lower in the control group (p = 0.016) and significantly higher in the CP group (p = 0.01). The CP group also had, in their nonstimulated PBMCs, significantly higher mRNA levels of inflammatory molecules: toll‐like receptor 4 (TLR‐4) (p = 0.0023), TNF‐α (p = 0.0016), transforming growth factor‐β–activated kinase 1 (p = 0.038), IκB kinase‐γ (p = 0.029), and c‐Jun N‐terminal kinase (p = 0.045). The TLR‐4 mRNA levels in the PBMCs were highly correlated with TNF‐α levels in LPS‐stimulated PBMCs (Spearman rank correlation = 0.38, p = 0.03).
Interpretation
The finding that preterm children with PVL‐induced CP have altered inflammatory responses indicates the possibility of programming effect of PVL or inflammation‐related events during early life. ANN NEUROL 2010;68:204–212 |
| doi_str_mv | 10.1002/ana.22049 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_888097724</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>748958784</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4249-97e9f24cfffe348abeab10dd0a1ee68ff018322277d2ef6b54eed89fc133a25c3</originalsourceid><addsrcrecordid>eNqF0U1r3DAQBmBRGppt2kP_QPGlhB6cjD5sSccl6SaBsCHQUuhFyPKIuJU_KnlJ999X6W6SU8lpQDwzI94h5AOFEwrATu1gTxgDoV-RBa04LRUT-jVZAK9FWVEuDsnblH4CgK4pvCGHDGpdAeULslqGGSO2RTf4YPvezmPcFhHTNA4JU34upoiZ9IW760IbcSjuu_mucLmriTYUkw1p-44c-Fzx_b4ekW-rL1_PLsvrm4urs-V16UT-Uqklas-E894jF8o2aBsKbQuWItbKe6CKM8akbBn6uqkEYqu0d5RzyyrHj8jxbu4Ux98bTLPpu-QwBDvguElGKQVaSiZelFIoXSmpHuTnnXRxTCmiN1Psehu3hoJ5yNfkfM2_fLP9uJ-6aXpsn-RjoBl82gObnA0-2sF16dlx0DQfJLvTnbvvAm7_v9Es18vH1eWuo0sz_nnqsPGXqSWXlfm-vjC357D-cVutzDn_CwWvoOE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>748958784</pqid></control><display><type>article</type><title>Altered inflammatory responses in preterm children with cerebral palsy</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Lin, Chang-Yi ; Chang, Ying-Chao ; Wang, Shan-Tair ; Lee, Ting-Yang ; Lin, Chiou-Feng ; Huang, Chao-Ching</creator><creatorcontrib>Lin, Chang-Yi ; Chang, Ying-Chao ; Wang, Shan-Tair ; Lee, Ting-Yang ; Lin, Chiou-Feng ; Huang, Chao-Ching</creatorcontrib><description>Objective
Perinatal inflammatory responses contribute to periventricular leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined whether preterm children with CP had altered inflammatory responses when school‐aged.
Methods
Thirty‐two preterm children with PVL‐induced CP (mean [±standard deviation] age, 7.2 ± 3.6 years) and 32 control preterm children with normal neurodevelopment (6.2 ± 2.2 years) and matched for gestational age were recruited. We measured tumor necrosis factor (TNF)‐α levels in the plasma and the supernatants of peripheral blood mononuclear cells (PBMCs) before and after lipopolysaccharide (LPS) stimulation, and proinflammatory gene expression in the PBMCs.
Results
TNF‐α expression was significantly higher in the plasma (p < 0.001) and supernatants of LPS‐stimulated PBMCs (p = 0.003) in the CP group than in the control group. After LPS stimulation, the intracellular TNF‐α level in the PBMCs was significantly lower in the control group (p = 0.016) and significantly higher in the CP group (p = 0.01). The CP group also had, in their nonstimulated PBMCs, significantly higher mRNA levels of inflammatory molecules: toll‐like receptor 4 (TLR‐4) (p = 0.0023), TNF‐α (p = 0.0016), transforming growth factor‐β–activated kinase 1 (p = 0.038), IκB kinase‐γ (p = 0.029), and c‐Jun N‐terminal kinase (p = 0.045). The TLR‐4 mRNA levels in the PBMCs were highly correlated with TNF‐α levels in LPS‐stimulated PBMCs (Spearman rank correlation = 0.38, p = 0.03).
Interpretation
The finding that preterm children with PVL‐induced CP have altered inflammatory responses indicates the possibility of programming effect of PVL or inflammation‐related events during early life. ANN NEUROL 2010;68:204–212</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.22049</identifier><identifier>PMID: 20695013</identifier><identifier>CODEN: ANNED3</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Biological and medical sciences ; Cerebral Palsy - blood ; Cerebral Palsy - immunology ; Cerebral Palsy - pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Inflammation - blood ; Inflammation - immunology ; Inflammation - pathology ; Inflammation Mediators - blood ; Inflammation Mediators - physiology ; Leukocytes, Mononuclear - metabolism ; Leukocytes, Mononuclear - pathology ; Lipopolysaccharides - pharmacology ; Male ; Medical sciences ; Neurology ; Pregnancy ; Premature Birth - blood ; Premature Birth - immunology ; Premature Birth - pathology ; Tumor Necrosis Factor-alpha - blood ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Annals of neurology, 2010-08, Vol.68 (2), p.204-212</ispartof><rights>Copyright © 2010 American Neurological Association</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4249-97e9f24cfffe348abeab10dd0a1ee68ff018322277d2ef6b54eed89fc133a25c3</citedby><cites>FETCH-LOGICAL-c4249-97e9f24cfffe348abeab10dd0a1ee68ff018322277d2ef6b54eed89fc133a25c3</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%2Fana.22049$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.22049$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23091134$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20695013$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Chang-Yi</creatorcontrib><creatorcontrib>Chang, Ying-Chao</creatorcontrib><creatorcontrib>Wang, Shan-Tair</creatorcontrib><creatorcontrib>Lee, Ting-Yang</creatorcontrib><creatorcontrib>Lin, Chiou-Feng</creatorcontrib><creatorcontrib>Huang, Chao-Ching</creatorcontrib><title>Altered inflammatory responses in preterm children with cerebral palsy</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
Perinatal inflammatory responses contribute to periventricular leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined whether preterm children with CP had altered inflammatory responses when school‐aged.
Methods
Thirty‐two preterm children with PVL‐induced CP (mean [±standard deviation] age, 7.2 ± 3.6 years) and 32 control preterm children with normal neurodevelopment (6.2 ± 2.2 years) and matched for gestational age were recruited. We measured tumor necrosis factor (TNF)‐α levels in the plasma and the supernatants of peripheral blood mononuclear cells (PBMCs) before and after lipopolysaccharide (LPS) stimulation, and proinflammatory gene expression in the PBMCs.
Results
TNF‐α expression was significantly higher in the plasma (p < 0.001) and supernatants of LPS‐stimulated PBMCs (p = 0.003) in the CP group than in the control group. After LPS stimulation, the intracellular TNF‐α level in the PBMCs was significantly lower in the control group (p = 0.016) and significantly higher in the CP group (p = 0.01). The CP group also had, in their nonstimulated PBMCs, significantly higher mRNA levels of inflammatory molecules: toll‐like receptor 4 (TLR‐4) (p = 0.0023), TNF‐α (p = 0.0016), transforming growth factor‐β–activated kinase 1 (p = 0.038), IκB kinase‐γ (p = 0.029), and c‐Jun N‐terminal kinase (p = 0.045). The TLR‐4 mRNA levels in the PBMCs were highly correlated with TNF‐α levels in LPS‐stimulated PBMCs (Spearman rank correlation = 0.38, p = 0.03).
Interpretation
The finding that preterm children with PVL‐induced CP have altered inflammatory responses indicates the possibility of programming effect of PVL or inflammation‐related events during early life. ANN NEUROL 2010;68:204–212</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Cerebral Palsy - blood</subject><subject>Cerebral Palsy - immunology</subject><subject>Cerebral Palsy - pathology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Inflammation - blood</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>Inflammation Mediators - blood</subject><subject>Inflammation Mediators - physiology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Leukocytes, Mononuclear - pathology</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Pregnancy</subject><subject>Premature Birth - blood</subject><subject>Premature Birth - immunology</subject><subject>Premature Birth - pathology</subject><subject>Tumor Necrosis Factor-alpha - blood</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U1r3DAQBmBRGppt2kP_QPGlhB6cjD5sSccl6SaBsCHQUuhFyPKIuJU_KnlJ999X6W6SU8lpQDwzI94h5AOFEwrATu1gTxgDoV-RBa04LRUT-jVZAK9FWVEuDsnblH4CgK4pvCGHDGpdAeULslqGGSO2RTf4YPvezmPcFhHTNA4JU34upoiZ9IW760IbcSjuu_mucLmriTYUkw1p-44c-Fzx_b4ekW-rL1_PLsvrm4urs-V16UT-Uqklas-E894jF8o2aBsKbQuWItbKe6CKM8akbBn6uqkEYqu0d5RzyyrHj8jxbu4Ux98bTLPpu-QwBDvguElGKQVaSiZelFIoXSmpHuTnnXRxTCmiN1Psehu3hoJ5yNfkfM2_fLP9uJ-6aXpsn-RjoBl82gObnA0-2sF16dlx0DQfJLvTnbvvAm7_v9Es18vH1eWuo0sz_nnqsPGXqSWXlfm-vjC357D-cVutzDn_CwWvoOE</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Lin, Chang-Yi</creator><creator>Chang, Ying-Chao</creator><creator>Wang, Shan-Tair</creator><creator>Lee, Ting-Yang</creator><creator>Lin, Chiou-Feng</creator><creator>Huang, Chao-Ching</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><scope>IQODW</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><scope>7TK</scope></search><sort><creationdate>201008</creationdate><title>Altered inflammatory responses in preterm children with cerebral palsy</title><author>Lin, Chang-Yi ; Chang, Ying-Chao ; Wang, Shan-Tair ; Lee, Ting-Yang ; Lin, Chiou-Feng ; Huang, Chao-Ching</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4249-97e9f24cfffe348abeab10dd0a1ee68ff018322277d2ef6b54eed89fc133a25c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Cerebral Palsy - blood</topic><topic>Cerebral Palsy - immunology</topic><topic>Cerebral Palsy - pathology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Inflammation - blood</topic><topic>Inflammation - immunology</topic><topic>Inflammation - pathology</topic><topic>Inflammation Mediators - blood</topic><topic>Inflammation Mediators - physiology</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Leukocytes, Mononuclear - pathology</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Pregnancy</topic><topic>Premature Birth - blood</topic><topic>Premature Birth - immunology</topic><topic>Premature Birth - pathology</topic><topic>Tumor Necrosis Factor-alpha - blood</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Chang-Yi</creatorcontrib><creatorcontrib>Chang, Ying-Chao</creatorcontrib><creatorcontrib>Wang, Shan-Tair</creatorcontrib><creatorcontrib>Lee, Ting-Yang</creatorcontrib><creatorcontrib>Lin, Chiou-Feng</creatorcontrib><creatorcontrib>Huang, Chao-Ching</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</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><collection>Neurosciences Abstracts</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Chang-Yi</au><au>Chang, Ying-Chao</au><au>Wang, Shan-Tair</au><au>Lee, Ting-Yang</au><au>Lin, Chiou-Feng</au><au>Huang, Chao-Ching</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered inflammatory responses in preterm children with cerebral palsy</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2010-08</date><risdate>2010</risdate><volume>68</volume><issue>2</issue><spage>204</spage><epage>212</epage><pages>204-212</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><coden>ANNED3</coden><abstract>Objective
Perinatal inflammatory responses contribute to periventricular leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined whether preterm children with CP had altered inflammatory responses when school‐aged.
Methods
Thirty‐two preterm children with PVL‐induced CP (mean [±standard deviation] age, 7.2 ± 3.6 years) and 32 control preterm children with normal neurodevelopment (6.2 ± 2.2 years) and matched for gestational age were recruited. We measured tumor necrosis factor (TNF)‐α levels in the plasma and the supernatants of peripheral blood mononuclear cells (PBMCs) before and after lipopolysaccharide (LPS) stimulation, and proinflammatory gene expression in the PBMCs.
Results
TNF‐α expression was significantly higher in the plasma (p < 0.001) and supernatants of LPS‐stimulated PBMCs (p = 0.003) in the CP group than in the control group. After LPS stimulation, the intracellular TNF‐α level in the PBMCs was significantly lower in the control group (p = 0.016) and significantly higher in the CP group (p = 0.01). The CP group also had, in their nonstimulated PBMCs, significantly higher mRNA levels of inflammatory molecules: toll‐like receptor 4 (TLR‐4) (p = 0.0023), TNF‐α (p = 0.0016), transforming growth factor‐β–activated kinase 1 (p = 0.038), IκB kinase‐γ (p = 0.029), and c‐Jun N‐terminal kinase (p = 0.045). The TLR‐4 mRNA levels in the PBMCs were highly correlated with TNF‐α levels in LPS‐stimulated PBMCs (Spearman rank correlation = 0.38, p = 0.03).
Interpretation
The finding that preterm children with PVL‐induced CP have altered inflammatory responses indicates the possibility of programming effect of PVL or inflammation‐related events during early life. ANN NEUROL 2010;68:204–212</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20695013</pmid><doi>10.1002/ana.22049</doi><tpages>9</tpages></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Biological and medical sciences Cerebral Palsy - blood Cerebral Palsy - immunology Cerebral Palsy - pathology Child Child, Preschool Female Humans Infant Infant, Newborn Inflammation - blood Inflammation - immunology Inflammation - pathology Inflammation Mediators - blood Inflammation Mediators - physiology Leukocytes, Mononuclear - metabolism Leukocytes, Mononuclear - pathology Lipopolysaccharides - pharmacology Male Medical sciences Neurology Pregnancy Premature Birth - blood Premature Birth - immunology Premature Birth - pathology Tumor Necrosis Factor-alpha - blood Vascular diseases and vascular malformations of the nervous system |
| title | Altered inflammatory responses in preterm children with cerebral palsy |
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