Hypothermia and erythropoietin for neuroprotection after neonatal brain damage
Background: Both hypothermia and erythropoietin (EPO) are reported to have neuroprotective effects after perinatal hypoxia–ischemia (HI). We investigated a possible additive effect of the use of a combination of hypothermia–EPO in a rat model of neonatal HI. Methods: At postnatal day 7, rats were su...
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| Veröffentlicht in: | Pediatric research 2013-01, Vol.73 (1), p.18-23 |
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| creator | Fan, Xiyong van Bel, Frank van der Kooij, Michael A. Heijnen, Cobi J. Groenendaal, Floris |
| description | Background:
Both hypothermia and erythropoietin (EPO) are reported to have neuroprotective effects after perinatal hypoxia–ischemia (HI). We investigated a possible additive effect of the use of a combination of hypothermia–EPO in a rat model of neonatal HI.
Methods:
At postnatal day 7, rats were subjected to HI and then randomized to 3 h of hypothermia, EPO, or both. Sensorimotor function was assessed by the cylinder-rearing test (CRT) at 2 and 5 wk after HI. Brain lesion volume and white matter loss were determined by hematoxylin–eosin and luxol fast blue staining, respectively.
Results:
Multivariable analysis using general linear modeling showed that hypothermia, EPO, and the interaction hypothermia × gender were determinants of sensorimotor function, both at 2 and 5 wk after HI. Neuroprotective effects of hypothermia at 5 wk were more pronounced in females, showing 52% improvement in the CRT. Maximal improvement in males was 26% after combined treatment with hypothermia and EPO. Histological outcome was improved by hypothermia only with no additional effect of EPO or gender.
Conclusion:
Hypothermia after HI improved sensorimotor function in females more than in males. There was a borderline additive effect of EPO when combined with hypothermia. Histology of brain lesion volume and white matter damage was improved only by hypothermia. |
| doi_str_mv | 10.1038/pr.2012.139 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1273324992</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1273324992</sourcerecordid><originalsourceid>FETCH-LOGICAL-c429t-fce48ff5e4072b25b5a2df2ae3d3ee6a5546adbfe82b912cf6968a8f732c08ca3</originalsourceid><addsrcrecordid>eNptkL1PwzAQxS0EoqUwsaOMSJDiryT2iCqgSBUsMEeX5NymSuJiO0P_e1wVmJhO9-6np3ePkGtG54wK9bBzc04ZnzOhT8iUZYKmVMrilEwpFSwVWqsJufB-SymTmZLnZMIFVZliekrelvudDRt0fQsJDE2Cbh82zu5si6EdEmNdMuAYBWcD1qG1QwIm4EG1AwTokspBBBvoYY2X5MxA5_HqZ87I5_PTx2KZrt5fXhePq7SWXIfU1CiVMRlKWvCKZ1UGvDEcUDQCMYcskzk0lUHFK814bXKdK1CmELymqgYxI7dH3xjra0Qfyr71NXYdxFijLxkvhOBSax7RuyNaO-u9Q1PuXNuD25eMlocC414eCixjgZG--TEeqx6bP_a3sQjcHwEfT8MaXbm1oxvis__6fQOkcnwI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1273324992</pqid></control><display><type>article</type><title>Hypothermia and erythropoietin for neuroprotection after neonatal brain damage</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Fan, Xiyong ; van Bel, Frank ; van der Kooij, Michael A. ; Heijnen, Cobi J. ; Groenendaal, Floris</creator><creatorcontrib>Fan, Xiyong ; van Bel, Frank ; van der Kooij, Michael A. ; Heijnen, Cobi J. ; Groenendaal, Floris</creatorcontrib><description>Background:
Both hypothermia and erythropoietin (EPO) are reported to have neuroprotective effects after perinatal hypoxia–ischemia (HI). We investigated a possible additive effect of the use of a combination of hypothermia–EPO in a rat model of neonatal HI.
Methods:
At postnatal day 7, rats were subjected to HI and then randomized to 3 h of hypothermia, EPO, or both. Sensorimotor function was assessed by the cylinder-rearing test (CRT) at 2 and 5 wk after HI. Brain lesion volume and white matter loss were determined by hematoxylin–eosin and luxol fast blue staining, respectively.
Results:
Multivariable analysis using general linear modeling showed that hypothermia, EPO, and the interaction hypothermia × gender were determinants of sensorimotor function, both at 2 and 5 wk after HI. Neuroprotective effects of hypothermia at 5 wk were more pronounced in females, showing 52% improvement in the CRT. Maximal improvement in males was 26% after combined treatment with hypothermia and EPO. Histological outcome was improved by hypothermia only with no additional effect of EPO or gender.
Conclusion:
Hypothermia after HI improved sensorimotor function in females more than in males. There was a borderline additive effect of EPO when combined with hypothermia. Histology of brain lesion volume and white matter damage was improved only by hypothermia.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/pr.2012.139</identifier><identifier>PMID: 23085819</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/154/436 ; 631/443/592/1939 ; 692/699/375/1345 ; 692/700/1720 ; Animals ; Animals, Newborn ; Blood Glucose ; Body Temperature ; Erythropoietin - therapeutic use ; Female ; Histological Techniques ; Hypothermia, Induced - methods ; Hypoxia-Ischemia, Brain - drug therapy ; Hypoxia-Ischemia, Brain - pathology ; Hypoxia-Ischemia, Brain - therapy ; Linear Models ; Male ; Medicine ; Medicine & Public Health ; Neuroprotective Agents - therapeutic use ; Pediatric Surgery ; Pediatrics ; Rats ; Sex Factors ; translational-investigation</subject><ispartof>Pediatric research, 2013-01, Vol.73 (1), p.18-23</ispartof><rights>International Pediatric Research Foundation, Inc. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-fce48ff5e4072b25b5a2df2ae3d3ee6a5546adbfe82b912cf6968a8f732c08ca3</citedby><cites>FETCH-LOGICAL-c429t-fce48ff5e4072b25b5a2df2ae3d3ee6a5546adbfe82b912cf6968a8f732c08ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/pr.2012.139$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/pr.2012.139$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23085819$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Xiyong</creatorcontrib><creatorcontrib>van Bel, Frank</creatorcontrib><creatorcontrib>van der Kooij, Michael A.</creatorcontrib><creatorcontrib>Heijnen, Cobi J.</creatorcontrib><creatorcontrib>Groenendaal, Floris</creatorcontrib><title>Hypothermia and erythropoietin for neuroprotection after neonatal brain damage</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background:
Both hypothermia and erythropoietin (EPO) are reported to have neuroprotective effects after perinatal hypoxia–ischemia (HI). We investigated a possible additive effect of the use of a combination of hypothermia–EPO in a rat model of neonatal HI.
Methods:
At postnatal day 7, rats were subjected to HI and then randomized to 3 h of hypothermia, EPO, or both. Sensorimotor function was assessed by the cylinder-rearing test (CRT) at 2 and 5 wk after HI. Brain lesion volume and white matter loss were determined by hematoxylin–eosin and luxol fast blue staining, respectively.
Results:
Multivariable analysis using general linear modeling showed that hypothermia, EPO, and the interaction hypothermia × gender were determinants of sensorimotor function, both at 2 and 5 wk after HI. Neuroprotective effects of hypothermia at 5 wk were more pronounced in females, showing 52% improvement in the CRT. Maximal improvement in males was 26% after combined treatment with hypothermia and EPO. Histological outcome was improved by hypothermia only with no additional effect of EPO or gender.
Conclusion:
Hypothermia after HI improved sensorimotor function in females more than in males. There was a borderline additive effect of EPO when combined with hypothermia. Histology of brain lesion volume and white matter damage was improved only by hypothermia.</description><subject>631/154/436</subject><subject>631/443/592/1939</subject><subject>692/699/375/1345</subject><subject>692/700/1720</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Blood Glucose</subject><subject>Body Temperature</subject><subject>Erythropoietin - therapeutic use</subject><subject>Female</subject><subject>Histological Techniques</subject><subject>Hypothermia, Induced - methods</subject><subject>Hypoxia-Ischemia, Brain - drug therapy</subject><subject>Hypoxia-Ischemia, Brain - pathology</subject><subject>Hypoxia-Ischemia, Brain - therapy</subject><subject>Linear Models</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Rats</subject><subject>Sex Factors</subject><subject>translational-investigation</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkL1PwzAQxS0EoqUwsaOMSJDiryT2iCqgSBUsMEeX5NymSuJiO0P_e1wVmJhO9-6np3ePkGtG54wK9bBzc04ZnzOhT8iUZYKmVMrilEwpFSwVWqsJufB-SymTmZLnZMIFVZliekrelvudDRt0fQsJDE2Cbh82zu5si6EdEmNdMuAYBWcD1qG1QwIm4EG1AwTokspBBBvoYY2X5MxA5_HqZ87I5_PTx2KZrt5fXhePq7SWXIfU1CiVMRlKWvCKZ1UGvDEcUDQCMYcskzk0lUHFK814bXKdK1CmELymqgYxI7dH3xjra0Qfyr71NXYdxFijLxkvhOBSax7RuyNaO-u9Q1PuXNuD25eMlocC414eCixjgZG--TEeqx6bP_a3sQjcHwEfT8MaXbm1oxvis__6fQOkcnwI</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Fan, Xiyong</creator><creator>van Bel, Frank</creator><creator>van der Kooij, Michael A.</creator><creator>Heijnen, Cobi J.</creator><creator>Groenendaal, Floris</creator><general>Nature Publishing Group US</general><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>20130101</creationdate><title>Hypothermia and erythropoietin for neuroprotection after neonatal brain damage</title><author>Fan, Xiyong ; van Bel, Frank ; van der Kooij, Michael A. ; Heijnen, Cobi J. ; Groenendaal, Floris</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-fce48ff5e4072b25b5a2df2ae3d3ee6a5546adbfe82b912cf6968a8f732c08ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/154/436</topic><topic>631/443/592/1939</topic><topic>692/699/375/1345</topic><topic>692/700/1720</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Blood Glucose</topic><topic>Body Temperature</topic><topic>Erythropoietin - therapeutic use</topic><topic>Female</topic><topic>Histological Techniques</topic><topic>Hypothermia, Induced - methods</topic><topic>Hypoxia-Ischemia, Brain - drug therapy</topic><topic>Hypoxia-Ischemia, Brain - pathology</topic><topic>Hypoxia-Ischemia, Brain - therapy</topic><topic>Linear Models</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Rats</topic><topic>Sex Factors</topic><topic>translational-investigation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Xiyong</creatorcontrib><creatorcontrib>van Bel, Frank</creatorcontrib><creatorcontrib>van der Kooij, Michael A.</creatorcontrib><creatorcontrib>Heijnen, Cobi J.</creatorcontrib><creatorcontrib>Groenendaal, Floris</creatorcontrib><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>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Xiyong</au><au>van Bel, Frank</au><au>van der Kooij, Michael A.</au><au>Heijnen, Cobi J.</au><au>Groenendaal, Floris</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypothermia and erythropoietin for neuroprotection after neonatal brain damage</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>73</volume><issue>1</issue><spage>18</spage><epage>23</epage><pages>18-23</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Background:
Both hypothermia and erythropoietin (EPO) are reported to have neuroprotective effects after perinatal hypoxia–ischemia (HI). We investigated a possible additive effect of the use of a combination of hypothermia–EPO in a rat model of neonatal HI.
Methods:
At postnatal day 7, rats were subjected to HI and then randomized to 3 h of hypothermia, EPO, or both. Sensorimotor function was assessed by the cylinder-rearing test (CRT) at 2 and 5 wk after HI. Brain lesion volume and white matter loss were determined by hematoxylin–eosin and luxol fast blue staining, respectively.
Results:
Multivariable analysis using general linear modeling showed that hypothermia, EPO, and the interaction hypothermia × gender were determinants of sensorimotor function, both at 2 and 5 wk after HI. Neuroprotective effects of hypothermia at 5 wk were more pronounced in females, showing 52% improvement in the CRT. Maximal improvement in males was 26% after combined treatment with hypothermia and EPO. Histological outcome was improved by hypothermia only with no additional effect of EPO or gender.
Conclusion:
Hypothermia after HI improved sensorimotor function in females more than in males. There was a borderline additive effect of EPO when combined with hypothermia. Histology of brain lesion volume and white matter damage was improved only by hypothermia.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>23085819</pmid><doi>10.1038/pr.2012.139</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/154/436 631/443/592/1939 692/699/375/1345 692/700/1720 Animals Animals, Newborn Blood Glucose Body Temperature Erythropoietin - therapeutic use Female Histological Techniques Hypothermia, Induced - methods Hypoxia-Ischemia, Brain - drug therapy Hypoxia-Ischemia, Brain - pathology Hypoxia-Ischemia, Brain - therapy Linear Models Male Medicine Medicine & Public Health Neuroprotective Agents - therapeutic use Pediatric Surgery Pediatrics Rats Sex Factors translational-investigation |
| title | Hypothermia and erythropoietin for neuroprotection after neonatal brain damage |
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