The metabolic representation of ischemia in rat brain slices: A hyperpolarized 13C magnetic resonance study
The ischemic penumbra in stroke is not clearly defined by today's available imaging tools. This study aimed to develop a model system and noninvasive biomarkers of ischemic brain tissue for an examination that might potentially be performed in humans, very quickly, in the course of stroke triag...
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| Veröffentlicht in: | NMR in biomedicine 2021-07, Vol.34 (7), p.n/a |
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| creator | Shaul, David Grieb, Benjamin Sapir, Gal Uppala, Sivaranjan Sosna, Jacob Gomori, J. Moshe Katz‐Brull, Rachel |
| description | The ischemic penumbra in stroke is not clearly defined by today's available imaging tools. This study aimed to develop a model system and noninvasive biomarkers of ischemic brain tissue for an examination that might potentially be performed in humans, very quickly, in the course of stroke triage. Perfused rat brain slices were used as a model system and 31P spectroscopy verified that the slices were able to recover from an ischemic insult of about 3.5 min of perfusion arrest. This was indicated as a return to physiological pH and adenosine triphosphate levels. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored and quantified by the metabolic conversions of hyperpolarized [1‐13C]pyruvate to [1‐13C]lactate and [13C]bicarbonate, respectively, using 13C spectroscopy. In a control group (n = 8), hyperpolarized [1‐13C]pyruvate was administered during continuous perfusion of the slices. In the ischemia group (n = 5), the perfusion was arrested 30 s prior to administration of hyperpolarized [1‐13C]pyruvate and perfusion was not resumed throughout the measurement time (approximately 3.5 min). Following about 110 s of the ischemic insult, LDH activity increased by 80.4 ± 13.5% and PDH activity decreased by 47.8 ± 25.3%. In the control group, the mean LDH/PDH ratio was 16.6 ± 3.3, and in the ischemia group, the LDH/PDH ratio reached an average value of 38.7 ± 16.9. The results suggest that monitoring the activity of LDH and PDH, and their relative activities, using hyperpolarized [1‐13C]pyruvate, could serve as an imaging biomarker to characterize the changes in the ischemic penumbra.
Perfused rat brain slices were used as a model system for the ischemic penumbra in stroke. pH and adenosine triphosphate levels, determined with 31P spectroscopy, verified that the slices were able to recover from an ischemic insult of about 3.5 min. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored following hyperpolarized [1‐13C]pyruvate administration with 13C spectroscopy. During an ischemic insult, LDH activity increased by 80.4% ± 13.5% and PDH activity decreased by 47.8% ± 25.3%. |
| doi_str_mv | 10.1002/nbm.4509 |
| format | Article |
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Perfused rat brain slices were used as a model system for the ischemic penumbra in stroke. pH and adenosine triphosphate levels, determined with 31P spectroscopy, verified that the slices were able to recover from an ischemic insult of about 3.5 min. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored following hyperpolarized [1‐13C]pyruvate administration with 13C spectroscopy. During an ischemic insult, LDH activity increased by 80.4% ± 13.5% and PDH activity decreased by 47.8% ± 25.3%.</description><identifier>ISSN: 0952-3480</identifier><identifier>EISSN: 1099-1492</identifier><identifier>DOI: 10.1002/nbm.4509</identifier><language>eng</language><publisher>Oxford: Wiley Subscription Services, Inc</publisher><subject>[1‐13C]pyruvate ; Adenosine triphosphate ; ATP ; Bicarbonates ; Biological products ; Biomarkers ; Brain ; Brain slice preparation ; Dehydrogenase ; Dehydrogenases ; hyperpolarized carbon‐13 ; Ischemia ; L-Lactate dehydrogenase ; Lactate dehydrogenase ; Lactic acid ; Magnetic resonance ; magnetic resonance spectroscopy ; Metabolism ; Neuroimaging ; Perfusion ; pyruvate dehydrogenase ; Pyruvic acid ; Spectroscopy ; Spectrum analysis</subject><ispartof>NMR in biomedicine, 2021-07, Vol.34 (7), p.n/a</ispartof><rights>2021 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-6267-5933 ; 0000-0002-6125-1984 ; 0000-0003-4850-1616</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fnbm.4509$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fnbm.4509$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Shaul, David</creatorcontrib><creatorcontrib>Grieb, Benjamin</creatorcontrib><creatorcontrib>Sapir, Gal</creatorcontrib><creatorcontrib>Uppala, Sivaranjan</creatorcontrib><creatorcontrib>Sosna, Jacob</creatorcontrib><creatorcontrib>Gomori, J. Moshe</creatorcontrib><creatorcontrib>Katz‐Brull, Rachel</creatorcontrib><title>The metabolic representation of ischemia in rat brain slices: A hyperpolarized 13C magnetic resonance study</title><title>NMR in biomedicine</title><description>The ischemic penumbra in stroke is not clearly defined by today's available imaging tools. This study aimed to develop a model system and noninvasive biomarkers of ischemic brain tissue for an examination that might potentially be performed in humans, very quickly, in the course of stroke triage. Perfused rat brain slices were used as a model system and 31P spectroscopy verified that the slices were able to recover from an ischemic insult of about 3.5 min of perfusion arrest. This was indicated as a return to physiological pH and adenosine triphosphate levels. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored and quantified by the metabolic conversions of hyperpolarized [1‐13C]pyruvate to [1‐13C]lactate and [13C]bicarbonate, respectively, using 13C spectroscopy. In a control group (n = 8), hyperpolarized [1‐13C]pyruvate was administered during continuous perfusion of the slices. In the ischemia group (n = 5), the perfusion was arrested 30 s prior to administration of hyperpolarized [1‐13C]pyruvate and perfusion was not resumed throughout the measurement time (approximately 3.5 min). Following about 110 s of the ischemic insult, LDH activity increased by 80.4 ± 13.5% and PDH activity decreased by 47.8 ± 25.3%. In the control group, the mean LDH/PDH ratio was 16.6 ± 3.3, and in the ischemia group, the LDH/PDH ratio reached an average value of 38.7 ± 16.9. The results suggest that monitoring the activity of LDH and PDH, and their relative activities, using hyperpolarized [1‐13C]pyruvate, could serve as an imaging biomarker to characterize the changes in the ischemic penumbra.
Perfused rat brain slices were used as a model system for the ischemic penumbra in stroke. pH and adenosine triphosphate levels, determined with 31P spectroscopy, verified that the slices were able to recover from an ischemic insult of about 3.5 min. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored following hyperpolarized [1‐13C]pyruvate administration with 13C spectroscopy. During an ischemic insult, LDH activity increased by 80.4% ± 13.5% and PDH activity decreased by 47.8% ± 25.3%.</description><subject>[1‐13C]pyruvate</subject><subject>Adenosine triphosphate</subject><subject>ATP</subject><subject>Bicarbonates</subject><subject>Biological products</subject><subject>Biomarkers</subject><subject>Brain</subject><subject>Brain slice preparation</subject><subject>Dehydrogenase</subject><subject>Dehydrogenases</subject><subject>hyperpolarized carbon‐13</subject><subject>Ischemia</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Magnetic resonance</subject><subject>magnetic resonance spectroscopy</subject><subject>Metabolism</subject><subject>Neuroimaging</subject><subject>Perfusion</subject><subject>pyruvate dehydrogenase</subject><subject>Pyruvic acid</subject><subject>Spectroscopy</subject><subject>Spectrum analysis</subject><issn>0952-3480</issn><issn>1099-1492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNotkF1LwzAUhoMoOKfgTwh43XmSNN3i3Rx-wdSb3YckPXWZbVqTDqm_3s559b4cHt4DDyHXDGYMgN8G28xyCeqETBgolbFc8VMyASV5JvIFnJOLlHYAsMgFn5DPzRZpg72xbe0djdhFTBh60_s20LaiPrktNt5QH2g0PbXRjC2NMKY7uqTbocPYtbWJ_gdLysSKNuYjYP-3ltpggkOa-n05XJKzytQJr_5zSjaPD5vVc7Z-f3pZLddZVxQqy52U1sgSVVWZRcFRcmsQYK5AWOlMCco5xZlT1jpjC7ZAsIKL8cQrMediSm6Os11sv_aYer1r9zGMHzWXYl4UIuf5SGVH6tvXOOgu-sbEQTPQB4161KgPGvXb_eshxS-nj2gc</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Shaul, David</creator><creator>Grieb, Benjamin</creator><creator>Sapir, Gal</creator><creator>Uppala, Sivaranjan</creator><creator>Sosna, Jacob</creator><creator>Gomori, J. Moshe</creator><creator>Katz‐Brull, Rachel</creator><general>Wiley Subscription Services, Inc</general><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0001-6267-5933</orcidid><orcidid>https://orcid.org/0000-0002-6125-1984</orcidid><orcidid>https://orcid.org/0000-0003-4850-1616</orcidid></search><sort><creationdate>202107</creationdate><title>The metabolic representation of ischemia in rat brain slices: A hyperpolarized 13C magnetic resonance study</title><author>Shaul, David ; Grieb, Benjamin ; Sapir, Gal ; Uppala, Sivaranjan ; Sosna, Jacob ; Gomori, J. Moshe ; Katz‐Brull, Rachel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p669-4c55ba5de9ffa862e52bae007903b5cad09cc921c9bbcab618e0b3239212f3723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>[1‐13C]pyruvate</topic><topic>Adenosine triphosphate</topic><topic>ATP</topic><topic>Bicarbonates</topic><topic>Biological products</topic><topic>Biomarkers</topic><topic>Brain</topic><topic>Brain slice preparation</topic><topic>Dehydrogenase</topic><topic>Dehydrogenases</topic><topic>hyperpolarized carbon‐13</topic><topic>Ischemia</topic><topic>L-Lactate dehydrogenase</topic><topic>Lactate dehydrogenase</topic><topic>Lactic acid</topic><topic>Magnetic resonance</topic><topic>magnetic resonance spectroscopy</topic><topic>Metabolism</topic><topic>Neuroimaging</topic><topic>Perfusion</topic><topic>pyruvate dehydrogenase</topic><topic>Pyruvic acid</topic><topic>Spectroscopy</topic><topic>Spectrum analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shaul, David</creatorcontrib><creatorcontrib>Grieb, Benjamin</creatorcontrib><creatorcontrib>Sapir, Gal</creatorcontrib><creatorcontrib>Uppala, Sivaranjan</creatorcontrib><creatorcontrib>Sosna, Jacob</creatorcontrib><creatorcontrib>Gomori, J. Moshe</creatorcontrib><creatorcontrib>Katz‐Brull, Rachel</creatorcontrib><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>NMR in biomedicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shaul, David</au><au>Grieb, Benjamin</au><au>Sapir, Gal</au><au>Uppala, Sivaranjan</au><au>Sosna, Jacob</au><au>Gomori, J. Moshe</au><au>Katz‐Brull, Rachel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The metabolic representation of ischemia in rat brain slices: A hyperpolarized 13C magnetic resonance study</atitle><jtitle>NMR in biomedicine</jtitle><date>2021-07</date><risdate>2021</risdate><volume>34</volume><issue>7</issue><epage>n/a</epage><issn>0952-3480</issn><eissn>1099-1492</eissn><abstract>The ischemic penumbra in stroke is not clearly defined by today's available imaging tools. This study aimed to develop a model system and noninvasive biomarkers of ischemic brain tissue for an examination that might potentially be performed in humans, very quickly, in the course of stroke triage. Perfused rat brain slices were used as a model system and 31P spectroscopy verified that the slices were able to recover from an ischemic insult of about 3.5 min of perfusion arrest. This was indicated as a return to physiological pH and adenosine triphosphate levels. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored and quantified by the metabolic conversions of hyperpolarized [1‐13C]pyruvate to [1‐13C]lactate and [13C]bicarbonate, respectively, using 13C spectroscopy. In a control group (n = 8), hyperpolarized [1‐13C]pyruvate was administered during continuous perfusion of the slices. In the ischemia group (n = 5), the perfusion was arrested 30 s prior to administration of hyperpolarized [1‐13C]pyruvate and perfusion was not resumed throughout the measurement time (approximately 3.5 min). Following about 110 s of the ischemic insult, LDH activity increased by 80.4 ± 13.5% and PDH activity decreased by 47.8 ± 25.3%. In the control group, the mean LDH/PDH ratio was 16.6 ± 3.3, and in the ischemia group, the LDH/PDH ratio reached an average value of 38.7 ± 16.9. The results suggest that monitoring the activity of LDH and PDH, and their relative activities, using hyperpolarized [1‐13C]pyruvate, could serve as an imaging biomarker to characterize the changes in the ischemic penumbra.
Perfused rat brain slices were used as a model system for the ischemic penumbra in stroke. pH and adenosine triphosphate levels, determined with 31P spectroscopy, verified that the slices were able to recover from an ischemic insult of about 3.5 min. Instantaneous changes in lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) activities were monitored following hyperpolarized [1‐13C]pyruvate administration with 13C spectroscopy. During an ischemic insult, LDH activity increased by 80.4% ± 13.5% and PDH activity decreased by 47.8% ± 25.3%.</abstract><cop>Oxford</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/nbm.4509</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-6267-5933</orcidid><orcidid>https://orcid.org/0000-0002-6125-1984</orcidid><orcidid>https://orcid.org/0000-0003-4850-1616</orcidid></addata></record> |
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| subjects | [1‐13C]pyruvate Adenosine triphosphate ATP Bicarbonates Biological products Biomarkers Brain Brain slice preparation Dehydrogenase Dehydrogenases hyperpolarized carbon‐13 Ischemia L-Lactate dehydrogenase Lactate dehydrogenase Lactic acid Magnetic resonance magnetic resonance spectroscopy Metabolism Neuroimaging Perfusion pyruvate dehydrogenase Pyruvic acid Spectroscopy Spectrum analysis |
| title | The metabolic representation of ischemia in rat brain slices: A hyperpolarized 13C magnetic resonance study |
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