Metabolite Profiling Identifies a Branched Chain Amino Acid Signature in Acute Cardioembolic Stroke
There is limited information about changes in metabolism during acute ischemic stroke. The identification of changes in circulating plasma metabolites during cerebral infarction may provide insight into disease pathogenesis and identify novel biomarkers. We performed filament occlusion of the middle...
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| Veröffentlicht in: | Stroke (1970) 2013-05, Vol.44 (5), p.1389-1395 |
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| creator | KIMBERLY, W. Taylor YU WANG PHAM, Ly FURIE, Karen L GERSZTEN, Robert E |
| description | There is limited information about changes in metabolism during acute ischemic stroke. The identification of changes in circulating plasma metabolites during cerebral infarction may provide insight into disease pathogenesis and identify novel biomarkers.
We performed filament occlusion of the middle cerebral artery of Wistar rats and collected plasma and cerebrospinal fluid 2 hours after the onset of ischemia. Plasma samples from control and patients with acute stroke were also analyzed. All samples were examined using liquid chromatography followed by tandem mass spectrometry. Positively charged metabolites, including amino acids, nucleotides, and neurotransmitters, were quantified using electrospray ionization followed by scheduled multiple reaction monitoring.
The concentrations of several metabolites were altered in the setting of cerebral ischemia. We detected a reduction in the branched chain amino acids (valine, leucine, isoleucine) in rat plasma, rat cerebrospinal fluid, and human plasma compared with respective controls (16%, 23%, and 17%, respectively; P |
| doi_str_mv | 10.1161/strokeaha.111.000397 |
| format | Article |
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We performed filament occlusion of the middle cerebral artery of Wistar rats and collected plasma and cerebrospinal fluid 2 hours after the onset of ischemia. Plasma samples from control and patients with acute stroke were also analyzed. All samples were examined using liquid chromatography followed by tandem mass spectrometry. Positively charged metabolites, including amino acids, nucleotides, and neurotransmitters, were quantified using electrospray ionization followed by scheduled multiple reaction monitoring.
The concentrations of several metabolites were altered in the setting of cerebral ischemia. We detected a reduction in the branched chain amino acids (valine, leucine, isoleucine) in rat plasma, rat cerebrospinal fluid, and human plasma compared with respective controls (16%, 23%, and 17%, respectively; P<0.01 for each). In patients, lower branched chain amino acids levels also correlated with poor neurological outcome (modified Rankin Scale, 0-2 versus 3-6; P=0.002).
Branched chain amino acids are reduced in ischemic stroke, and the degree of reduction correlates with worse neurological outcome. Whether branched chain amino acids are in a causal pathway or are an epiphenomenon of ischemic stroke remains to be determined.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/strokeaha.111.000397</identifier><identifier>PMID: 23520238</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Amino Acids, Branched-Chain - blood ; Amino Acids, Branched-Chain - cerebrospinal fluid ; Animals ; Biological and medical sciences ; Biomarkers - blood ; Biomarkers - cerebrospinal fluid ; Brain Ischemia - blood ; Brain Ischemia - cerebrospinal fluid ; Female ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Humans ; Male ; Mass Spectrometry ; Medical sciences ; Nervous system (semeiology, syndromes) ; Neurology ; Rats ; Rats, Wistar ; Stroke - blood ; Stroke - cerebrospinal fluid ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Stroke (1970), 2013-05, Vol.44 (5), p.1389-1395</ispartof><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-f824134b5b5db684ca21069b346e6ffee22d325d0c537b4a80ad8098033c54773</citedby><cites>FETCH-LOGICAL-c555t-f824134b5b5db684ca21069b346e6ffee22d325d0c537b4a80ad8098033c54773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,3676,27911,27912</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27321623$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23520238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KIMBERLY, W. Taylor</creatorcontrib><creatorcontrib>YU WANG</creatorcontrib><creatorcontrib>PHAM, Ly</creatorcontrib><creatorcontrib>FURIE, Karen L</creatorcontrib><creatorcontrib>GERSZTEN, Robert E</creatorcontrib><title>Metabolite Profiling Identifies a Branched Chain Amino Acid Signature in Acute Cardioembolic Stroke</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>There is limited information about changes in metabolism during acute ischemic stroke. The identification of changes in circulating plasma metabolites during cerebral infarction may provide insight into disease pathogenesis and identify novel biomarkers.
We performed filament occlusion of the middle cerebral artery of Wistar rats and collected plasma and cerebrospinal fluid 2 hours after the onset of ischemia. Plasma samples from control and patients with acute stroke were also analyzed. All samples were examined using liquid chromatography followed by tandem mass spectrometry. Positively charged metabolites, including amino acids, nucleotides, and neurotransmitters, were quantified using electrospray ionization followed by scheduled multiple reaction monitoring.
The concentrations of several metabolites were altered in the setting of cerebral ischemia. We detected a reduction in the branched chain amino acids (valine, leucine, isoleucine) in rat plasma, rat cerebrospinal fluid, and human plasma compared with respective controls (16%, 23%, and 17%, respectively; P<0.01 for each). In patients, lower branched chain amino acids levels also correlated with poor neurological outcome (modified Rankin Scale, 0-2 versus 3-6; P=0.002).
Branched chain amino acids are reduced in ischemic stroke, and the degree of reduction correlates with worse neurological outcome. Whether branched chain amino acids are in a causal pathway or are an epiphenomenon of ischemic stroke remains to be determined.</description><subject>Adult</subject><subject>Amino Acids, Branched-Chain - blood</subject><subject>Amino Acids, Branched-Chain - cerebrospinal fluid</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - cerebrospinal fluid</subject><subject>Brain Ischemia - blood</subject><subject>Brain Ischemia - cerebrospinal fluid</subject><subject>Female</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Humans</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Stroke - blood</subject><subject>Stroke - cerebrospinal fluid</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1u1DAUhS0EokPhDRDyBqmbFP8mzgYpjFpaUVTElLV1YzszhiQudlKpb4_DDKVd2ff6u8fHPgi9peSU0pJ-SFMMvxzsIJf0lBDC6-oZWlHJRCFKpp6j1dIrmKjrI_QqpZ-ZYVzJl-iIccmW_QqZr26CNvR-cvhbDJ3v_bjFl9aNk--8Sxjwpwij2TmL1zvwI24GPwbcGG_xxm9HmObo8NI3c9ZYQ7Q-uGGRNHjz1-Nr9KKDPrk3h_UY_Tg_u1lfFFfXny_XzVVhpJRT0SkmKBetbKVtSyUMMErKuuWidGXXOceY5UxaYiSvWgGKgFWkVoRzI0VV8WP0ca97O7eDsya_IUKvb6MfIN7rAF4_PRn9Tm_DneaKlkTVWeDkIBDD79mlSQ8-Gdf3MLowJ53dSUmrul5QsUdNDClF1z1cQ4le8tGbm-_XX86aiyaXVO_zyWPvHlt8GPoXSAbeHwBIBvpu-Xuf_nMVZ7RknP8BNQybGw</recordid><startdate>20130501</startdate><enddate>20130501</enddate><creator>KIMBERLY, W. Taylor</creator><creator>YU WANG</creator><creator>PHAM, Ly</creator><creator>FURIE, Karen L</creator><creator>GERSZTEN, Robert E</creator><general>Lippincott Williams & Wilkins</general><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>5PM</scope></search><sort><creationdate>20130501</creationdate><title>Metabolite Profiling Identifies a Branched Chain Amino Acid Signature in Acute Cardioembolic Stroke</title><author>KIMBERLY, W. Taylor ; YU WANG ; PHAM, Ly ; FURIE, Karen L ; GERSZTEN, Robert E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-f824134b5b5db684ca21069b346e6ffee22d325d0c537b4a80ad8098033c54773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Amino Acids, Branched-Chain - blood</topic><topic>Amino Acids, Branched-Chain - cerebrospinal fluid</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - cerebrospinal fluid</topic><topic>Brain Ischemia - blood</topic><topic>Brain Ischemia - cerebrospinal fluid</topic><topic>Female</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>Humans</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Stroke - blood</topic><topic>Stroke - cerebrospinal fluid</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KIMBERLY, W. Taylor</creatorcontrib><creatorcontrib>YU WANG</creatorcontrib><creatorcontrib>PHAM, Ly</creatorcontrib><creatorcontrib>FURIE, Karen L</creatorcontrib><creatorcontrib>GERSZTEN, Robert E</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KIMBERLY, W. Taylor</au><au>YU WANG</au><au>PHAM, Ly</au><au>FURIE, Karen L</au><au>GERSZTEN, Robert E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolite Profiling Identifies a Branched Chain Amino Acid Signature in Acute Cardioembolic Stroke</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2013-05-01</date><risdate>2013</risdate><volume>44</volume><issue>5</issue><spage>1389</spage><epage>1395</epage><pages>1389-1395</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>There is limited information about changes in metabolism during acute ischemic stroke. The identification of changes in circulating plasma metabolites during cerebral infarction may provide insight into disease pathogenesis and identify novel biomarkers.
We performed filament occlusion of the middle cerebral artery of Wistar rats and collected plasma and cerebrospinal fluid 2 hours after the onset of ischemia. Plasma samples from control and patients with acute stroke were also analyzed. All samples were examined using liquid chromatography followed by tandem mass spectrometry. Positively charged metabolites, including amino acids, nucleotides, and neurotransmitters, were quantified using electrospray ionization followed by scheduled multiple reaction monitoring.
The concentrations of several metabolites were altered in the setting of cerebral ischemia. We detected a reduction in the branched chain amino acids (valine, leucine, isoleucine) in rat plasma, rat cerebrospinal fluid, and human plasma compared with respective controls (16%, 23%, and 17%, respectively; P<0.01 for each). In patients, lower branched chain amino acids levels also correlated with poor neurological outcome (modified Rankin Scale, 0-2 versus 3-6; P=0.002).
Branched chain amino acids are reduced in ischemic stroke, and the degree of reduction correlates with worse neurological outcome. Whether branched chain amino acids are in a causal pathway or are an epiphenomenon of ischemic stroke remains to be determined.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>23520238</pmid><doi>10.1161/strokeaha.111.000397</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Amino Acids, Branched-Chain - blood Amino Acids, Branched-Chain - cerebrospinal fluid Animals Biological and medical sciences Biomarkers - blood Biomarkers - cerebrospinal fluid Brain Ischemia - blood Brain Ischemia - cerebrospinal fluid Female Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Humans Male Mass Spectrometry Medical sciences Nervous system (semeiology, syndromes) Neurology Rats Rats, Wistar Stroke - blood Stroke - cerebrospinal fluid Vascular diseases and vascular malformations of the nervous system |
| title | Metabolite Profiling Identifies a Branched Chain Amino Acid Signature in Acute Cardioembolic Stroke |
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