Tetramethylpyrazine Nitrone Reduces Oxidative Stress to Alleviate Cerebral Vasospasm in Experimental Subarachnoid Hemorrhage Models
Cerebral vasospasm is one of the deleterious complications after subarachnoid hemorrhage (SAH), leading to delayed cerebral ischemia and permanent neurological deficits or even death. Free radicals and oxidative stress are considered as crucial causes contributing to cerebral vasospasm and brain dam...
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| Veröffentlicht in: | Neuromolecular medicine 2019-09, Vol.21 (3), p.262-274 |
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| creator | Wu, Liangmiao Su, Zhiyang Zha, Ling Zhu, Zeyu Liu, Wei Sun, Yewei Yu, Pei Wang, Yuqiang Zhang, Gaoxiao Zhang, Zaijun |
| description | Cerebral vasospasm is one of the deleterious complications after subarachnoid hemorrhage (SAH), leading to delayed cerebral ischemia and permanent neurological deficits or even death. Free radicals and oxidative stress are considered as crucial causes contributing to cerebral vasospasm and brain damage after SAH. Tetramethylpyrazine nitrone (TBN), a derivative of the clinically used anti-stroke drug tetramethylpyrazine armed with a powerful free radical scavenging nitrone moiety, has been reported to prevent brain damage from ischemic stroke. The present study aimed to investigate the effects of TBN on vasospasm and brain damage after SAH. Two experimental SAH models were used, a rat model by endovascular perforation and a rabbit model by intracisternal injection of autologous blood. The effects of TBN on SAH were evaluated assessing basilar artery spasm, neuronal apoptosis, and neurological deficits. TBN treatment significantly attenuated vasospasm, improved neurological behavior functions and reduced the number of apoptotic neurons in both the SAH rats and rabbits. Mechanistically, TBN suppressed the increase in 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine immuno-positive cells in the cortex of SAH rat brain. Western blot analyses indicated that TBN effectively reversed the altered expression of Bcl-2, Bax and cytochrome C, and up-regulated nuclear factor erythroid-derived 2-like 2 (Nrf2) and hemeoxygenase-1 (HO-1) protein expressions. In the in vitro studies, TBN inhibited H
2
O
2
-induced bEnd.3 cell apoptosis and reduced ROS generation. Additionally, TBN alleviated the contraction of rat basilar artery rings induced by H
2
O
2
ex vivo. In conclusion, TBN ameliorated SAH-induced cerebral vasospasm and neuronal damage. These effects of TBN may be attributed to its anti-oxidative stress effect and up-regulation of Nrf2/HO-1. |
| doi_str_mv | 10.1007/s12017-019-08543-9 |
| format | Article |
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2
O
2
-induced bEnd.3 cell apoptosis and reduced ROS generation. Additionally, TBN alleviated the contraction of rat basilar artery rings induced by H
2
O
2
ex vivo. In conclusion, TBN ameliorated SAH-induced cerebral vasospasm and neuronal damage. These effects of TBN may be attributed to its anti-oxidative stress effect and up-regulation of Nrf2/HO-1.</description><identifier>ISSN: 1535-1084</identifier><identifier>EISSN: 1559-1174</identifier><identifier>DOI: 10.1007/s12017-019-08543-9</identifier><identifier>PMID: 31134485</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aneurysms ; Animal models ; Animals ; Antioxidants - therapeutic use ; Apoptosis ; Apoptosis - drug effects ; Basilar Artery - drug effects ; Bax protein ; Bcl-2 protein ; Biomedical and Life Sciences ; Biomedicine ; Brain damage ; Brain Damage, Chronic - etiology ; Brain Damage, Chronic - prevention & control ; Brain injury ; Cardiovascular system ; Cerebral Cortex - pathology ; Contraction ; Cytochrome c ; Deoxyguanosine ; Disease Models, Animal ; Free radicals ; Free Radicals - metabolism ; Gene Expression Regulation - drug effects ; Heme Oxygenase (Decyclizing) - physiology ; Hippocampus - pathology ; Hydrogen peroxide ; Hydrogen Peroxide - pharmacology ; Internal Medicine ; Ischemia ; Isometric Contraction ; Male ; Nerve Tissue Proteins - biosynthesis ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - physiology ; Neurological diseases ; Neurology ; Neurosciences ; NF-E2-Related Factor 2 - physiology ; Nitrotyrosine ; Original Paper ; Oxidative stress ; Oxidative Stress - drug effects ; Pyrazines - therapeutic use ; Rabbits ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species - metabolism ; Stroke ; Subarachnoid hemorrhage ; Subarachnoid Hemorrhage - complications ; Subarachnoid Hemorrhage - metabolism ; Vasoconstriction ; Vasospasm, Intracranial - drug therapy ; Vasospasm, Intracranial - etiology</subject><ispartof>Neuromolecular medicine, 2019-09, Vol.21 (3), p.262-274</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>NeuroMolecular Medicine is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-363c8eb757b68f3cd1e2ed75cf49c72d216fe6e806227f339d31056f2a71bc023</citedby><cites>FETCH-LOGICAL-c441t-363c8eb757b68f3cd1e2ed75cf49c72d216fe6e806227f339d31056f2a71bc023</cites><orcidid>0000-0002-0690-1673</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12017-019-08543-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12017-019-08543-9$$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/31134485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Liangmiao</creatorcontrib><creatorcontrib>Su, Zhiyang</creatorcontrib><creatorcontrib>Zha, Ling</creatorcontrib><creatorcontrib>Zhu, Zeyu</creatorcontrib><creatorcontrib>Liu, Wei</creatorcontrib><creatorcontrib>Sun, Yewei</creatorcontrib><creatorcontrib>Yu, Pei</creatorcontrib><creatorcontrib>Wang, Yuqiang</creatorcontrib><creatorcontrib>Zhang, Gaoxiao</creatorcontrib><creatorcontrib>Zhang, Zaijun</creatorcontrib><title>Tetramethylpyrazine Nitrone Reduces Oxidative Stress to Alleviate Cerebral Vasospasm in Experimental Subarachnoid Hemorrhage Models</title><title>Neuromolecular medicine</title><addtitle>Neuromol Med</addtitle><addtitle>Neuromolecular Med</addtitle><description>Cerebral vasospasm is one of the deleterious complications after subarachnoid hemorrhage (SAH), leading to delayed cerebral ischemia and permanent neurological deficits or even death. Free radicals and oxidative stress are considered as crucial causes contributing to cerebral vasospasm and brain damage after SAH. Tetramethylpyrazine nitrone (TBN), a derivative of the clinically used anti-stroke drug tetramethylpyrazine armed with a powerful free radical scavenging nitrone moiety, has been reported to prevent brain damage from ischemic stroke. The present study aimed to investigate the effects of TBN on vasospasm and brain damage after SAH. Two experimental SAH models were used, a rat model by endovascular perforation and a rabbit model by intracisternal injection of autologous blood. The effects of TBN on SAH were evaluated assessing basilar artery spasm, neuronal apoptosis, and neurological deficits. TBN treatment significantly attenuated vasospasm, improved neurological behavior functions and reduced the number of apoptotic neurons in both the SAH rats and rabbits. Mechanistically, TBN suppressed the increase in 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine immuno-positive cells in the cortex of SAH rat brain. Western blot analyses indicated that TBN effectively reversed the altered expression of Bcl-2, Bax and cytochrome C, and up-regulated nuclear factor erythroid-derived 2-like 2 (Nrf2) and hemeoxygenase-1 (HO-1) protein expressions. In the in vitro studies, TBN inhibited H
2
O
2
-induced bEnd.3 cell apoptosis and reduced ROS generation. Additionally, TBN alleviated the contraction of rat basilar artery rings induced by H
2
O
2
ex vivo. In conclusion, TBN ameliorated SAH-induced cerebral vasospasm and neuronal damage. These effects of TBN may be attributed to its anti-oxidative stress effect and up-regulation of Nrf2/HO-1.</description><subject>Aneurysms</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antioxidants - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Basilar Artery - drug effects</subject><subject>Bax protein</subject><subject>Bcl-2 protein</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain damage</subject><subject>Brain Damage, Chronic - etiology</subject><subject>Brain Damage, Chronic - prevention & control</subject><subject>Brain injury</subject><subject>Cardiovascular system</subject><subject>Cerebral Cortex - pathology</subject><subject>Contraction</subject><subject>Cytochrome c</subject><subject>Deoxyguanosine</subject><subject>Disease Models, Animal</subject><subject>Free radicals</subject><subject>Free Radicals - metabolism</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Heme Oxygenase (Decyclizing) - physiology</subject><subject>Hippocampus - pathology</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Internal Medicine</subject><subject>Ischemia</subject><subject>Isometric Contraction</subject><subject>Male</subject><subject>Nerve Tissue Proteins - biosynthesis</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>Neurological diseases</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>NF-E2-Related Factor 2 - physiology</subject><subject>Nitrotyrosine</subject><subject>Original Paper</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Pyrazines - therapeutic use</subject><subject>Rabbits</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Stroke</subject><subject>Subarachnoid hemorrhage</subject><subject>Subarachnoid Hemorrhage - complications</subject><subject>Subarachnoid Hemorrhage - metabolism</subject><subject>Vasoconstriction</subject><subject>Vasospasm, Intracranial - drug therapy</subject><subject>Vasospasm, Intracranial - etiology</subject><issn>1535-1084</issn><issn>1559-1174</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kE9P3DAQxa2qqPxpv0APyFLPoR47iZMjWkFBokUC2qvl2BM2KImD7azYXvni9bJbuHGakd6b9zQ_Qr4COwHG5PcAnIHMGNQZq4pcZPUHcgBFUWcAMv-42UWRAavyfXIYwgNjnAPAJ7IvAESeV8UBeb7D6PWAcbnup7XXf7sR6a8uepfmDdrZYKDXT53VsVshvY0eQ6DR0dO-x1WnI9IFemy87ukfHVyYdBhoN9Kzpwl9N-AYk3I7N9prsxxdZ-kFDs77pb5H-tNZ7MNnstfqPuCX3Twiv8_P7hYX2dX1j8vF6VVm8hxiJkphKmxkIZuyaoWxgBytLEyb10Zyy6FsscSKlZzLVojaCmBF2XItoTGMiyPybZs7efc4Y4jqwc1-TJWKc8ESD4AyufjWZbwLwWOrpvSH9msFTG24qy13lbirF-6qTkfHu-i5GdC-nvwHnQxiawhJGu_Rv3W_E_sPNQCQOw</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Wu, Liangmiao</creator><creator>Su, Zhiyang</creator><creator>Zha, Ling</creator><creator>Zhu, Zeyu</creator><creator>Liu, Wei</creator><creator>Sun, Yewei</creator><creator>Yu, Pei</creator><creator>Wang, Yuqiang</creator><creator>Zhang, Gaoxiao</creator><creator>Zhang, Zaijun</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-0690-1673</orcidid></search><sort><creationdate>20190901</creationdate><title>Tetramethylpyrazine Nitrone Reduces Oxidative Stress to Alleviate Cerebral Vasospasm in Experimental Subarachnoid Hemorrhage Models</title><author>Wu, Liangmiao ; Su, Zhiyang ; Zha, Ling ; Zhu, Zeyu ; Liu, Wei ; Sun, Yewei ; Yu, Pei ; Wang, Yuqiang ; Zhang, Gaoxiao ; Zhang, Zaijun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-363c8eb757b68f3cd1e2ed75cf49c72d216fe6e806227f339d31056f2a71bc023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aneurysms</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antioxidants - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Basilar Artery - drug effects</topic><topic>Bax protein</topic><topic>Bcl-2 protein</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain damage</topic><topic>Brain Damage, Chronic - etiology</topic><topic>Brain Damage, Chronic - prevention & control</topic><topic>Brain injury</topic><topic>Cardiovascular system</topic><topic>Cerebral Cortex - pathology</topic><topic>Contraction</topic><topic>Cytochrome c</topic><topic>Deoxyguanosine</topic><topic>Disease Models, Animal</topic><topic>Free radicals</topic><topic>Free Radicals - metabolism</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Heme Oxygenase (Decyclizing) - physiology</topic><topic>Hippocampus - pathology</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Internal Medicine</topic><topic>Ischemia</topic><topic>Isometric Contraction</topic><topic>Male</topic><topic>Nerve Tissue Proteins - biosynthesis</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>Neurological diseases</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>NF-E2-Related Factor 2 - physiology</topic><topic>Nitrotyrosine</topic><topic>Original Paper</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Pyrazines - therapeutic use</topic><topic>Rabbits</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Stroke</topic><topic>Subarachnoid hemorrhage</topic><topic>Subarachnoid Hemorrhage - complications</topic><topic>Subarachnoid Hemorrhage - metabolism</topic><topic>Vasoconstriction</topic><topic>Vasospasm, Intracranial - drug therapy</topic><topic>Vasospasm, Intracranial - etiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Liangmiao</creatorcontrib><creatorcontrib>Su, Zhiyang</creatorcontrib><creatorcontrib>Zha, Ling</creatorcontrib><creatorcontrib>Zhu, Zeyu</creatorcontrib><creatorcontrib>Liu, Wei</creatorcontrib><creatorcontrib>Sun, Yewei</creatorcontrib><creatorcontrib>Yu, Pei</creatorcontrib><creatorcontrib>Wang, Yuqiang</creatorcontrib><creatorcontrib>Zhang, Gaoxiao</creatorcontrib><creatorcontrib>Zhang, Zaijun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biotechnology and BioEngineering Abstracts</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 Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><jtitle>Neuromolecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Liangmiao</au><au>Su, Zhiyang</au><au>Zha, Ling</au><au>Zhu, Zeyu</au><au>Liu, Wei</au><au>Sun, Yewei</au><au>Yu, Pei</au><au>Wang, Yuqiang</au><au>Zhang, Gaoxiao</au><au>Zhang, Zaijun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tetramethylpyrazine Nitrone Reduces Oxidative Stress to Alleviate Cerebral Vasospasm in Experimental Subarachnoid Hemorrhage Models</atitle><jtitle>Neuromolecular medicine</jtitle><stitle>Neuromol Med</stitle><addtitle>Neuromolecular Med</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>21</volume><issue>3</issue><spage>262</spage><epage>274</epage><pages>262-274</pages><issn>1535-1084</issn><eissn>1559-1174</eissn><abstract>Cerebral vasospasm is one of the deleterious complications after subarachnoid hemorrhage (SAH), leading to delayed cerebral ischemia and permanent neurological deficits or even death. Free radicals and oxidative stress are considered as crucial causes contributing to cerebral vasospasm and brain damage after SAH. Tetramethylpyrazine nitrone (TBN), a derivative of the clinically used anti-stroke drug tetramethylpyrazine armed with a powerful free radical scavenging nitrone moiety, has been reported to prevent brain damage from ischemic stroke. The present study aimed to investigate the effects of TBN on vasospasm and brain damage after SAH. Two experimental SAH models were used, a rat model by endovascular perforation and a rabbit model by intracisternal injection of autologous blood. The effects of TBN on SAH were evaluated assessing basilar artery spasm, neuronal apoptosis, and neurological deficits. TBN treatment significantly attenuated vasospasm, improved neurological behavior functions and reduced the number of apoptotic neurons in both the SAH rats and rabbits. Mechanistically, TBN suppressed the increase in 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine immuno-positive cells in the cortex of SAH rat brain. Western blot analyses indicated that TBN effectively reversed the altered expression of Bcl-2, Bax and cytochrome C, and up-regulated nuclear factor erythroid-derived 2-like 2 (Nrf2) and hemeoxygenase-1 (HO-1) protein expressions. In the in vitro studies, TBN inhibited H
2
O
2
-induced bEnd.3 cell apoptosis and reduced ROS generation. Additionally, TBN alleviated the contraction of rat basilar artery rings induced by H
2
O
2
ex vivo. In conclusion, TBN ameliorated SAH-induced cerebral vasospasm and neuronal damage. These effects of TBN may be attributed to its anti-oxidative stress effect and up-regulation of Nrf2/HO-1.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31134485</pmid><doi>10.1007/s12017-019-08543-9</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-0690-1673</orcidid></addata></record> |
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| ispartof | Neuromolecular medicine, 2019-09, Vol.21 (3), p.262-274 |
| issn | 1535-1084 1559-1174 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Aneurysms Animal models Animals Antioxidants - therapeutic use Apoptosis Apoptosis - drug effects Basilar Artery - drug effects Bax protein Bcl-2 protein Biomedical and Life Sciences Biomedicine Brain damage Brain Damage, Chronic - etiology Brain Damage, Chronic - prevention & control Brain injury Cardiovascular system Cerebral Cortex - pathology Contraction Cytochrome c Deoxyguanosine Disease Models, Animal Free radicals Free Radicals - metabolism Gene Expression Regulation - drug effects Heme Oxygenase (Decyclizing) - physiology Hippocampus - pathology Hydrogen peroxide Hydrogen Peroxide - pharmacology Internal Medicine Ischemia Isometric Contraction Male Nerve Tissue Proteins - biosynthesis Nerve Tissue Proteins - genetics Nerve Tissue Proteins - physiology Neurological diseases Neurology Neurosciences NF-E2-Related Factor 2 - physiology Nitrotyrosine Original Paper Oxidative stress Oxidative Stress - drug effects Pyrazines - therapeutic use Rabbits Random Allocation Rats Rats, Sprague-Dawley Reactive Oxygen Species - metabolism Stroke Subarachnoid hemorrhage Subarachnoid Hemorrhage - complications Subarachnoid Hemorrhage - metabolism Vasoconstriction Vasospasm, Intracranial - drug therapy Vasospasm, Intracranial - etiology |
| title | Tetramethylpyrazine Nitrone Reduces Oxidative Stress to Alleviate Cerebral Vasospasm in Experimental Subarachnoid Hemorrhage Models |
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