Unique brain region-dependent cytokine signatures after prolonged hypothermic cardiac arrest in rats.
Identifieur interne : 000242 ( Main/Exploration ); précédent : 000241; suivant : 000243Unique brain region-dependent cytokine signatures after prolonged hypothermic cardiac arrest in rats.
Auteurs : Tomas Drabek [États-Unis] ; Caleb D. Wilson ; Andreas Janata ; Jason P. Stezoski ; Keri Janesko-Feldman ; Robert H. Garman ; Samuel A. Tisherman ; Patrick M. KochanekSource :
- Therapeutic hypothermia and temperature management [ 2153-7933 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Arrêt cardiaque (physiopathologie), Arrêt cardiaque provoqué (), Cytokines (métabolisme), Encéphale (métabolisme), Facteurs temps, Hypothermie (physiopathologie), Hypothermie provoquée (), Maladies du système nerveux (physiopathologie), Maladies du système nerveux (étiologie), Mâle, Pontage cardiopulmonaire (), Rat Sprague-Dawley, Réanimation cardiopulmonaire (), Technique d'immunofluorescence.
- MESH :
- métabolisme : Cytokines, Encéphale.
- physiopathologie : Arrêt cardiaque, Hypothermie, Maladies du système nerveux.
- étiologie : Maladies du système nerveux.
- Animaux, Arrêt cardiaque provoqué, Facteurs temps, Hypothermie provoquée, Mâle, Pontage cardiopulmonaire, Rat Sprague-Dawley, Réanimation cardiopulmonaire, Technique d'immunofluorescence.
English descriptors
- KwdEn :
- Animals, Brain (metabolism), Cardiopulmonary Bypass (methods), Cardiopulmonary Resuscitation (methods), Cytokines (metabolism), Fluorescent Antibody Technique, Heart Arrest (physiopathology), Heart Arrest, Induced (methods), Hypothermia (physiopathology), Hypothermia, Induced (methods), Male, Nervous System Diseases (etiology), Nervous System Diseases (physiopathology), Rats, Sprague-Dawley, Time Factors.
- MESH :
- chemical , metabolism : Cytokines.
- etiology : Nervous System Diseases.
- metabolism : Brain.
- methods : Cardiopulmonary Bypass, Cardiopulmonary Resuscitation, Heart Arrest, Induced, Hypothermia, Induced.
- physiopathology : Heart Arrest, Hypothermia, Nervous System Diseases.
- Animals, Fluorescent Antibody Technique, Male, Rats, Sprague-Dawley, Time Factors.
Abstract
We previously showed that prolonged cardiac arrest (CA) produces neuronal death with microglial proliferation. Microglial proliferation, but not neuronal death, was attenuated by deeper hypothermia. Microglia are reportedly a major source of cytokines. In this study, we tested the hypotheses that (1) CA will result in highly specific regional and temporal increases in brain cytokines; and (2) these increases will be attenuated by deep hypothermia. Adult male Sprague-Dawley rats were subjected to rapid exsanguination. After 6 minutes of normothermic no-flow, different levels of hypothermia were induced by either ice-cold (IC) or room-temperature (RT) aortic flush. After 20 minutes CA, rats were resuscitated with cardiopulmonary bypass (CPB), and sacrificed at 6 or 24 hours. Rats subjected to CPB only (without CA) and shams (no CPB or CA) served as controls (n=6 per group). Cytokines were analyzed in cerebellum, cortex, hippocampus, and striatum. Immunofluorescence was used to identify cell types associated with individual cytokines. Intra-CA temperature was lower after IC versus RT flush (21°C vs. 28°C, p<0.05). At 6 hours, striatum showed a massive increase in interleukin (IL)-1α and tumor necrosis factor-alpha (TNF-α) (>100-fold higher than in hippocampus), which was attenuated by deeper hypothermia in the IC versus RT group. In contrast, IL-12 was 50-fold higher in hippocampus versus striatum. At 24 hours, cytokines decreased. In striatum, IL-1α colocalized with astrocytes while TNF-α colocalized with neurons. In hippocampus, IL-12 colocalized with hippocampal hilar neurons, the only region where neuronal degeneration was observed at 24 hours at both IC and RT groups. We report important temporo-spatial differences in the brain cytokine response to hypothermic CA, with a novel role of striatum. Astrocytes and neurons, but not microglia colocalized with individual cytokines. Hypothermia showed protective effects. These neuroinflammatory reactions precede neuronal death. New therapeutic strategies may need to target early regional neuroinflammation.
DOI: 10.1089/ther.2014.0013
PubMed: 25423415
Affiliations:
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Le document en format XML
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<term>Brain (metabolism)</term>
<term>Cardiopulmonary Bypass (methods)</term>
<term>Cardiopulmonary Resuscitation (methods)</term>
<term>Cytokines (metabolism)</term>
<term>Fluorescent Antibody Technique</term>
<term>Heart Arrest (physiopathology)</term>
<term>Heart Arrest, Induced (methods)</term>
<term>Hypothermia (physiopathology)</term>
<term>Hypothermia, Induced (methods)</term>
<term>Male</term>
<term>Nervous System Diseases (etiology)</term>
<term>Nervous System Diseases (physiopathology)</term>
<term>Rats, Sprague-Dawley</term>
<term>Time Factors</term>
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<term>Arrêt cardiaque (physiopathologie)</term>
<term>Arrêt cardiaque provoqué ()</term>
<term>Cytokines (métabolisme)</term>
<term>Encéphale (métabolisme)</term>
<term>Facteurs temps</term>
<term>Hypothermie (physiopathologie)</term>
<term>Hypothermie provoquée ()</term>
<term>Maladies du système nerveux (physiopathologie)</term>
<term>Maladies du système nerveux (étiologie)</term>
<term>Mâle</term>
<term>Pontage cardiopulmonaire ()</term>
<term>Rat Sprague-Dawley</term>
<term>Réanimation cardiopulmonaire ()</term>
<term>Technique d'immunofluorescence</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term>
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<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Cardiopulmonary Bypass</term>
<term>Cardiopulmonary Resuscitation</term>
<term>Heart Arrest, Induced</term>
<term>Hypothermia, Induced</term>
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<term>Encéphale</term>
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<term>Hypothermie</term>
<term>Maladies du système nerveux</term>
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<term>Hypothermia</term>
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<term>Hypothermie provoquée</term>
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<front><div type="abstract" xml:lang="en">We previously showed that prolonged cardiac arrest (CA) produces neuronal death with microglial proliferation. Microglial proliferation, but not neuronal death, was attenuated by deeper hypothermia. Microglia are reportedly a major source of cytokines. In this study, we tested the hypotheses that (1) CA will result in highly specific regional and temporal increases in brain cytokines; and (2) these increases will be attenuated by deep hypothermia. Adult male Sprague-Dawley rats were subjected to rapid exsanguination. After 6 minutes of normothermic no-flow, different levels of hypothermia were induced by either ice-cold (IC) or room-temperature (RT) aortic flush. After 20 minutes CA, rats were resuscitated with cardiopulmonary bypass (CPB), and sacrificed at 6 or 24 hours. Rats subjected to CPB only (without CA) and shams (no CPB or CA) served as controls (n=6 per group). Cytokines were analyzed in cerebellum, cortex, hippocampus, and striatum. Immunofluorescence was used to identify cell types associated with individual cytokines. Intra-CA temperature was lower after IC versus RT flush (21°C vs. 28°C, p<0.05). At 6 hours, striatum showed a massive increase in interleukin (IL)-1α and tumor necrosis factor-alpha (TNF-α) (>100-fold higher than in hippocampus), which was attenuated by deeper hypothermia in the IC versus RT group. In contrast, IL-12 was 50-fold higher in hippocampus versus striatum. At 24 hours, cytokines decreased. In striatum, IL-1α colocalized with astrocytes while TNF-α colocalized with neurons. In hippocampus, IL-12 colocalized with hippocampal hilar neurons, the only region where neuronal degeneration was observed at 24 hours at both IC and RT groups. We report important temporo-spatial differences in the brain cytokine response to hypothermic CA, with a novel role of striatum. Astrocytes and neurons, but not microglia colocalized with individual cytokines. Hypothermia showed protective effects. These neuroinflammatory reactions precede neuronal death. New therapeutic strategies may need to target early regional neuroinflammation.</div>
</front>
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<name sortKey="Janata, Andreas" sort="Janata, Andreas" uniqKey="Janata A" first="Andreas" last="Janata">Andreas Janata</name>
<name sortKey="Janesko Feldman, Keri" sort="Janesko Feldman, Keri" uniqKey="Janesko Feldman K" first="Keri" last="Janesko-Feldman">Keri Janesko-Feldman</name>
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<name sortKey="Stezoski, Jason P" sort="Stezoski, Jason P" uniqKey="Stezoski J" first="Jason P" last="Stezoski">Jason P. Stezoski</name>
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<country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Drabek, Tomas" sort="Drabek, Tomas" uniqKey="Drabek T" first="Tomas" last="Drabek">Tomas Drabek</name>
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