Optimum therapeutic hypothermia temperature after perinatal asphyxia: a magnetic resonance spectroscopy biomarker and immunohistochemistry study in the newborn piglet
Abstract Background Therapeutic hypothermia for neonatal encephalopathy improves survival with normal neurological outcome. Despite treatment, however, 50% of infants have adverse outcomes; customising cooling with more precision might provide further benefit. The specific brain temperature for opti...
Gespeichert in:
| Veröffentlicht in: | The Lancet (British edition) 2014-02, Vol.383, p.S54-S54 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | S54 |
|---|---|
| container_issue | |
| container_start_page | S54 |
| container_title | The Lancet (British edition) |
| container_volume | 383 |
| creator | Hassell, Jane K, Dr Chandrasekaran, Mani, MBBS Faulkner, Stuart D, PhD Bainbridge, Alan, PhD Fleiss, Bobbi, PhD Bennett, Kate Cady, Ern, PhD Raivich, Gennadij, Prof Gressens, Pierre, Prof Golay, Xavier, Prof Robertson, Nicola J, Prof |
| description | Abstract Background Therapeutic hypothermia for neonatal encephalopathy improves survival with normal neurological outcome. Despite treatment, however, 50% of infants have adverse outcomes; customising cooling with more precision might provide further benefit. The specific brain temperature for optimum neuroprotection is unknown. We have previously shown in the piglet that optimum neuroprotection by delayed cooling occurs at different temperatures in the cortical (33°C) and deep grey (35°C) matter. Magnetic resonance biomarkers, including lactate:creatine ratio (Lac/Cr), predict neurodevelopmental outcome after neonatal encephalopathy. We aimed to assess the optimum temperature for regional neuroprotection in a proton magnetic resonance system (1H MRS). Methods 28 male piglets aged less than 24 h were anaesthetised with isoflurane and underwent trachaeal intubation, ventilation, continuous physiological monitoring, and intensive care treatment to maintain sedation and physiological homoeostasis. Within the bore of our 9·4 T magnetic resonance system all piglets underwent a hypoxic-ischaemic insult for 12·5 min, measured with real-time phosphorous MRS, before resuscitation. After this insult piglets were randomised (seven in each group) to normothermia (38·5°C), hypothermia (35°C), hypothermia (33·5°C), and hypothermia (30°C). Serial MRS assessments were acquired before, during, and up to 48 h after transient cerebral hypoxia-ischaemia. Areas under the curve (AUC) for the 1H MRS Lac/Cr peak-area ratio in ventromedial forebrain (vmFB, predominantly grey matter) and dorsal subcortical (dsc, predominantly white matter) voxels were calculated. Programmed cell death at 48 h was measured with terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining on paraffin-embedded tissue in corresponding regions. Findings Compared with normothermia, cooling to 35°C and 33·5°C produced consistent 50–75% reduction in density of TUNEL-positive cells with significant decreases in insular cortex, hippocampus, subcortical white matter, thalamus, and putamen (p |
| doi_str_mv | 10.1016/S0140-6736(14)60317-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1501846536</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0140673614603172</els_id><sourcerecordid>3229535161</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2322-5bc3cef13f814a6f346202fd364dcfba2531ad19127090a1abee81cab39712743</originalsourceid><addsrcrecordid>eNqFUcuO1DAQjBBIDAufgGSJCxwCfsWZ4QBarXhJK-0BkLhZHaez8W5iG9sB8kN8J84MAokLp1bbVdVdXVX1mNHnjDL14iNlktaqFeopk88UFayt-Z1qx2Qr60a2X-5Wuz-Q-9WDlG4opVLRZlf9vArZzstM8ogRAi7ZGjKuwW_9bIFknEP5yUtEAkPGSEprHWSYCKQwrj8svCRAZrh2uJEjJu_AGSQpoMnRJ-PDSjrrZ4i3hQ-uJ3aeF-dHm7I3I86lxpWkvPQrsW7bhTj83vnoSLDXE-aH1b0BpoSPftez6vPbN58u3teXV-8-XJxf1oYLzuumM8LgwMSwZxLUIKTilA-9ULI3Qwe8EQx6dmC8pQcKDDrEPTPQiUNb3qQ4q56cdEP0XxdMWd_4JboyUrOGsr1UjVAF1ZxQprhLEQcdoi3uVs2o3iLRx0j0dm_NpD5GonnhvT7xsFj4ZjHqZCyWU_U2llPp3tv_Krz6R8FM1lkD0y2umP4uqxPX9CSyaTB5VODiFxL-rYk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1501846536</pqid></control><display><type>article</type><title>Optimum therapeutic hypothermia temperature after perinatal asphyxia: a magnetic resonance spectroscopy biomarker and immunohistochemistry study in the newborn piglet</title><source>Access via ScienceDirect (Elsevier)</source><source>ProQuest Central UK/Ireland</source><creator>Hassell, Jane K, Dr ; Chandrasekaran, Mani, MBBS ; Faulkner, Stuart D, PhD ; Bainbridge, Alan, PhD ; Fleiss, Bobbi, PhD ; Bennett, Kate ; Cady, Ern, PhD ; Raivich, Gennadij, Prof ; Gressens, Pierre, Prof ; Golay, Xavier, Prof ; Robertson, Nicola J, Prof</creator><creatorcontrib>Hassell, Jane K, Dr ; Chandrasekaran, Mani, MBBS ; Faulkner, Stuart D, PhD ; Bainbridge, Alan, PhD ; Fleiss, Bobbi, PhD ; Bennett, Kate ; Cady, Ern, PhD ; Raivich, Gennadij, Prof ; Gressens, Pierre, Prof ; Golay, Xavier, Prof ; Robertson, Nicola J, Prof</creatorcontrib><description>Abstract Background Therapeutic hypothermia for neonatal encephalopathy improves survival with normal neurological outcome. Despite treatment, however, 50% of infants have adverse outcomes; customising cooling with more precision might provide further benefit. The specific brain temperature for optimum neuroprotection is unknown. We have previously shown in the piglet that optimum neuroprotection by delayed cooling occurs at different temperatures in the cortical (33°C) and deep grey (35°C) matter. Magnetic resonance biomarkers, including lactate:creatine ratio (Lac/Cr), predict neurodevelopmental outcome after neonatal encephalopathy. We aimed to assess the optimum temperature for regional neuroprotection in a proton magnetic resonance system (1H MRS). Methods 28 male piglets aged less than 24 h were anaesthetised with isoflurane and underwent trachaeal intubation, ventilation, continuous physiological monitoring, and intensive care treatment to maintain sedation and physiological homoeostasis. Within the bore of our 9·4 T magnetic resonance system all piglets underwent a hypoxic-ischaemic insult for 12·5 min, measured with real-time phosphorous MRS, before resuscitation. After this insult piglets were randomised (seven in each group) to normothermia (38·5°C), hypothermia (35°C), hypothermia (33·5°C), and hypothermia (30°C). Serial MRS assessments were acquired before, during, and up to 48 h after transient cerebral hypoxia-ischaemia. Areas under the curve (AUC) for the 1H MRS Lac/Cr peak-area ratio in ventromedial forebrain (vmFB, predominantly grey matter) and dorsal subcortical (dsc, predominantly white matter) voxels were calculated. Programmed cell death at 48 h was measured with terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining on paraffin-embedded tissue in corresponding regions. Findings Compared with normothermia, cooling to 35°C and 33·5°C produced consistent 50–75% reduction in density of TUNEL-positive cells with significant decreases in insular cortex, hippocampus, subcortical white matter, thalamus, and putamen (p<0·05 in ANOVA and post-hoc Tukey test). Cooling to 30°C did not further reduce TUNEL-positive cell density compared with 33·5°C and 35°C in dorsal parietal cortex (dCTX); more cell death was seen in the deep grey matter (thalamus and putamen) at 30°C. MRS biomarker analysis did not show an increase in Lac/Cr AUC in the vmFB voxel at 30°C compared with 33·5° and 35°C (p=0·07). Raised Lac/Cr and increased cell death at 30°C was not seen in the dsc voxel or in dCTX. Interpretation Cooling to 30°C worsened hypoxic-ischaemic injury in the thalamus and basal ganglia compared with cooling to 33·5°C and 35°C. We showed a higher threshold optimum temperature for neuroprotection in the deep grey matter than in white matter/dCTX on the basis of immunohistochemical markers of cell death. Systemic effects of cooling to 30°C might have exacerbated these detrimental effects on deep grey matter cell death. These data support previous work in the developing brain and are relevant to clinical practice for optimum therapeutic hypothermia in newborn infants with birth asphyxia. Funding UK Medical Research Council, National Institute for Health Research.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(14)60317-2</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Cooling ; Hypothermia ; Hypoxia ; Infants ; Internal Medicine ; Medical research ; Mortality ; Physiology ; Variance analysis</subject><ispartof>The Lancet (British edition), 2014-02, Vol.383, p.S54-S54</ispartof><rights>Elsevier Ltd</rights><rights>2014 Elsevier Ltd</rights><rights>Copyright Elsevier Limited Feb 26, 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1501846536?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64389,72469</link.rule.ids></links><search><creatorcontrib>Hassell, Jane K, Dr</creatorcontrib><creatorcontrib>Chandrasekaran, Mani, MBBS</creatorcontrib><creatorcontrib>Faulkner, Stuart D, PhD</creatorcontrib><creatorcontrib>Bainbridge, Alan, PhD</creatorcontrib><creatorcontrib>Fleiss, Bobbi, PhD</creatorcontrib><creatorcontrib>Bennett, Kate</creatorcontrib><creatorcontrib>Cady, Ern, PhD</creatorcontrib><creatorcontrib>Raivich, Gennadij, Prof</creatorcontrib><creatorcontrib>Gressens, Pierre, Prof</creatorcontrib><creatorcontrib>Golay, Xavier, Prof</creatorcontrib><creatorcontrib>Robertson, Nicola J, Prof</creatorcontrib><title>Optimum therapeutic hypothermia temperature after perinatal asphyxia: a magnetic resonance spectroscopy biomarker and immunohistochemistry study in the newborn piglet</title><title>The Lancet (British edition)</title><description>Abstract Background Therapeutic hypothermia for neonatal encephalopathy improves survival with normal neurological outcome. Despite treatment, however, 50% of infants have adverse outcomes; customising cooling with more precision might provide further benefit. The specific brain temperature for optimum neuroprotection is unknown. We have previously shown in the piglet that optimum neuroprotection by delayed cooling occurs at different temperatures in the cortical (33°C) and deep grey (35°C) matter. Magnetic resonance biomarkers, including lactate:creatine ratio (Lac/Cr), predict neurodevelopmental outcome after neonatal encephalopathy. We aimed to assess the optimum temperature for regional neuroprotection in a proton magnetic resonance system (1H MRS). Methods 28 male piglets aged less than 24 h were anaesthetised with isoflurane and underwent trachaeal intubation, ventilation, continuous physiological monitoring, and intensive care treatment to maintain sedation and physiological homoeostasis. Within the bore of our 9·4 T magnetic resonance system all piglets underwent a hypoxic-ischaemic insult for 12·5 min, measured with real-time phosphorous MRS, before resuscitation. After this insult piglets were randomised (seven in each group) to normothermia (38·5°C), hypothermia (35°C), hypothermia (33·5°C), and hypothermia (30°C). Serial MRS assessments were acquired before, during, and up to 48 h after transient cerebral hypoxia-ischaemia. Areas under the curve (AUC) for the 1H MRS Lac/Cr peak-area ratio in ventromedial forebrain (vmFB, predominantly grey matter) and dorsal subcortical (dsc, predominantly white matter) voxels were calculated. Programmed cell death at 48 h was measured with terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining on paraffin-embedded tissue in corresponding regions. Findings Compared with normothermia, cooling to 35°C and 33·5°C produced consistent 50–75% reduction in density of TUNEL-positive cells with significant decreases in insular cortex, hippocampus, subcortical white matter, thalamus, and putamen (p<0·05 in ANOVA and post-hoc Tukey test). Cooling to 30°C did not further reduce TUNEL-positive cell density compared with 33·5°C and 35°C in dorsal parietal cortex (dCTX); more cell death was seen in the deep grey matter (thalamus and putamen) at 30°C. MRS biomarker analysis did not show an increase in Lac/Cr AUC in the vmFB voxel at 30°C compared with 33·5° and 35°C (p=0·07). Raised Lac/Cr and increased cell death at 30°C was not seen in the dsc voxel or in dCTX. Interpretation Cooling to 30°C worsened hypoxic-ischaemic injury in the thalamus and basal ganglia compared with cooling to 33·5°C and 35°C. We showed a higher threshold optimum temperature for neuroprotection in the deep grey matter than in white matter/dCTX on the basis of immunohistochemical markers of cell death. Systemic effects of cooling to 30°C might have exacerbated these detrimental effects on deep grey matter cell death. These data support previous work in the developing brain and are relevant to clinical practice for optimum therapeutic hypothermia in newborn infants with birth asphyxia. Funding UK Medical Research Council, National Institute for Health Research.</description><subject>Cooling</subject><subject>Hypothermia</subject><subject>Hypoxia</subject><subject>Infants</subject><subject>Internal Medicine</subject><subject>Medical research</subject><subject>Mortality</subject><subject>Physiology</subject><subject>Variance analysis</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFUcuO1DAQjBBIDAufgGSJCxwCfsWZ4QBarXhJK-0BkLhZHaez8W5iG9sB8kN8J84MAokLp1bbVdVdXVX1mNHnjDL14iNlktaqFeopk88UFayt-Z1qx2Qr60a2X-5Wuz-Q-9WDlG4opVLRZlf9vArZzstM8ogRAi7ZGjKuwW_9bIFknEP5yUtEAkPGSEprHWSYCKQwrj8svCRAZrh2uJEjJu_AGSQpoMnRJ-PDSjrrZ4i3hQ-uJ3aeF-dHm7I3I86lxpWkvPQrsW7bhTj83vnoSLDXE-aH1b0BpoSPftez6vPbN58u3teXV-8-XJxf1oYLzuumM8LgwMSwZxLUIKTilA-9ULI3Qwe8EQx6dmC8pQcKDDrEPTPQiUNb3qQ4q56cdEP0XxdMWd_4JboyUrOGsr1UjVAF1ZxQprhLEQcdoi3uVs2o3iLRx0j0dm_NpD5GonnhvT7xsFj4ZjHqZCyWU_U2llPp3tv_Krz6R8FM1lkD0y2umP4uqxPX9CSyaTB5VODiFxL-rYk</recordid><startdate>20140226</startdate><enddate>20140226</enddate><creator>Hassell, Jane K, Dr</creator><creator>Chandrasekaran, Mani, MBBS</creator><creator>Faulkner, Stuart D, PhD</creator><creator>Bainbridge, Alan, PhD</creator><creator>Fleiss, Bobbi, PhD</creator><creator>Bennett, Kate</creator><creator>Cady, Ern, PhD</creator><creator>Raivich, Gennadij, Prof</creator><creator>Gressens, Pierre, Prof</creator><creator>Golay, Xavier, Prof</creator><creator>Robertson, Nicola J, Prof</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>AAYXX</scope><scope>CITATION</scope><scope>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope></search><sort><creationdate>20140226</creationdate><title>Optimum therapeutic hypothermia temperature after perinatal asphyxia: a magnetic resonance spectroscopy biomarker and immunohistochemistry study in the newborn piglet</title><author>Hassell, Jane K, Dr ; Chandrasekaran, Mani, MBBS ; Faulkner, Stuart D, PhD ; Bainbridge, Alan, PhD ; Fleiss, Bobbi, PhD ; Bennett, Kate ; Cady, Ern, PhD ; Raivich, Gennadij, Prof ; Gressens, Pierre, Prof ; Golay, Xavier, Prof ; Robertson, Nicola J, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2322-5bc3cef13f814a6f346202fd364dcfba2531ad19127090a1abee81cab39712743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Cooling</topic><topic>Hypothermia</topic><topic>Hypoxia</topic><topic>Infants</topic><topic>Internal Medicine</topic><topic>Medical research</topic><topic>Mortality</topic><topic>Physiology</topic><topic>Variance analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hassell, Jane K, Dr</creatorcontrib><creatorcontrib>Chandrasekaran, Mani, MBBS</creatorcontrib><creatorcontrib>Faulkner, Stuart D, PhD</creatorcontrib><creatorcontrib>Bainbridge, Alan, PhD</creatorcontrib><creatorcontrib>Fleiss, Bobbi, PhD</creatorcontrib><creatorcontrib>Bennett, Kate</creatorcontrib><creatorcontrib>Cady, Ern, PhD</creatorcontrib><creatorcontrib>Raivich, Gennadij, Prof</creatorcontrib><creatorcontrib>Gressens, Pierre, Prof</creatorcontrib><creatorcontrib>Golay, Xavier, Prof</creatorcontrib><creatorcontrib>Robertson, Nicola J, Prof</creatorcontrib><collection>CrossRef</collection><collection>News PRO</collection><collection>Pharma and Biotech Premium PRO</collection><collection>Global News & ABI/Inform Professional</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Newsstand Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hassell, Jane K, Dr</au><au>Chandrasekaran, Mani, MBBS</au><au>Faulkner, Stuart D, PhD</au><au>Bainbridge, Alan, PhD</au><au>Fleiss, Bobbi, PhD</au><au>Bennett, Kate</au><au>Cady, Ern, PhD</au><au>Raivich, Gennadij, Prof</au><au>Gressens, Pierre, Prof</au><au>Golay, Xavier, Prof</au><au>Robertson, Nicola J, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimum therapeutic hypothermia temperature after perinatal asphyxia: a magnetic resonance spectroscopy biomarker and immunohistochemistry study in the newborn piglet</atitle><jtitle>The Lancet (British edition)</jtitle><date>2014-02-26</date><risdate>2014</risdate><volume>383</volume><spage>S54</spage><epage>S54</epage><pages>S54-S54</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Abstract Background Therapeutic hypothermia for neonatal encephalopathy improves survival with normal neurological outcome. Despite treatment, however, 50% of infants have adverse outcomes; customising cooling with more precision might provide further benefit. The specific brain temperature for optimum neuroprotection is unknown. We have previously shown in the piglet that optimum neuroprotection by delayed cooling occurs at different temperatures in the cortical (33°C) and deep grey (35°C) matter. Magnetic resonance biomarkers, including lactate:creatine ratio (Lac/Cr), predict neurodevelopmental outcome after neonatal encephalopathy. We aimed to assess the optimum temperature for regional neuroprotection in a proton magnetic resonance system (1H MRS). Methods 28 male piglets aged less than 24 h were anaesthetised with isoflurane and underwent trachaeal intubation, ventilation, continuous physiological monitoring, and intensive care treatment to maintain sedation and physiological homoeostasis. Within the bore of our 9·4 T magnetic resonance system all piglets underwent a hypoxic-ischaemic insult for 12·5 min, measured with real-time phosphorous MRS, before resuscitation. After this insult piglets were randomised (seven in each group) to normothermia (38·5°C), hypothermia (35°C), hypothermia (33·5°C), and hypothermia (30°C). Serial MRS assessments were acquired before, during, and up to 48 h after transient cerebral hypoxia-ischaemia. Areas under the curve (AUC) for the 1H MRS Lac/Cr peak-area ratio in ventromedial forebrain (vmFB, predominantly grey matter) and dorsal subcortical (dsc, predominantly white matter) voxels were calculated. Programmed cell death at 48 h was measured with terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining on paraffin-embedded tissue in corresponding regions. Findings Compared with normothermia, cooling to 35°C and 33·5°C produced consistent 50–75% reduction in density of TUNEL-positive cells with significant decreases in insular cortex, hippocampus, subcortical white matter, thalamus, and putamen (p<0·05 in ANOVA and post-hoc Tukey test). Cooling to 30°C did not further reduce TUNEL-positive cell density compared with 33·5°C and 35°C in dorsal parietal cortex (dCTX); more cell death was seen in the deep grey matter (thalamus and putamen) at 30°C. MRS biomarker analysis did not show an increase in Lac/Cr AUC in the vmFB voxel at 30°C compared with 33·5° and 35°C (p=0·07). Raised Lac/Cr and increased cell death at 30°C was not seen in the dsc voxel or in dCTX. Interpretation Cooling to 30°C worsened hypoxic-ischaemic injury in the thalamus and basal ganglia compared with cooling to 33·5°C and 35°C. We showed a higher threshold optimum temperature for neuroprotection in the deep grey matter than in white matter/dCTX on the basis of immunohistochemical markers of cell death. Systemic effects of cooling to 30°C might have exacerbated these detrimental effects on deep grey matter cell death. These data support previous work in the developing brain and are relevant to clinical practice for optimum therapeutic hypothermia in newborn infants with birth asphyxia. Funding UK Medical Research Council, National Institute for Health Research.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><doi>10.1016/S0140-6736(14)60317-2</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2014-02, Vol.383, p.S54-S54 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_journals_1501846536 |
| source | Access via ScienceDirect (Elsevier); ProQuest Central UK/Ireland |
| subjects | Cooling Hypothermia Hypoxia Infants Internal Medicine Medical research Mortality Physiology Variance analysis |
| title | Optimum therapeutic hypothermia temperature after perinatal asphyxia: a magnetic resonance spectroscopy biomarker and immunohistochemistry study in the newborn piglet |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T15%3A59%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Optimum%20therapeutic%20hypothermia%20temperature%20after%20perinatal%20asphyxia:%20a%20magnetic%20resonance%20spectroscopy%20biomarker%20and%20immunohistochemistry%20study%20in%20the%20newborn%20piglet&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Hassell,%20Jane%20K,%20Dr&rft.date=2014-02-26&rft.volume=383&rft.spage=S54&rft.epage=S54&rft.pages=S54-S54&rft.issn=0140-6736&rft.eissn=1474-547X&rft.coden=LANCAO&rft_id=info:doi/10.1016/S0140-6736(14)60317-2&rft_dat=%3Cproquest_cross%3E3229535161%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1501846536&rft_id=info:pmid/&rft_els_id=1_s2_0_S0140673614603172&rfr_iscdi=true |