Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3β signaling pathway
Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Neuronal apoptosis is involved in the pathological process of EBI. Hydrogen can inhibit neuronal apoptosis and attenuate EBI following SAH. However, the molecular mechanism underlying hydrogen-mediated an...
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| Veröffentlicht in: | PloS one 2014-04, Vol.9 (4), p.e96212 |
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| description | Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Neuronal apoptosis is involved in the pathological process of EBI. Hydrogen can inhibit neuronal apoptosis and attenuate EBI following SAH. However, the molecular mechanism underlying hydrogen-mediated anti-apoptotic effects in SAH has not been elucidated. In the present study, we aimed to evaluate whether hydrogen alleviates EBI after SAH, specifically neuronal apoptosis, partially via the Akt/GSK3β signaling pathway.
Sprague-Dawley rats (n = 85) were randomly divided into the following groups: sham group (n = 17), SAH group (n = 17), SAH + saline group (n = 17), SAH + hydrogen-rich saline (HS) group (n = 17) and SAH + HS + Ly294002 (n = 17) group. HS or an equal volume of physiological saline was administered immediately after surgery and repeated 8 hours later. The PI3K inhibitor, Ly294002, was applied to manipulate the proposed pathway. Neurological score and SAH grade were assessed at 24 hours after SAH. Western blot was used for the quantification of Akt, pAkt, GSK3β, pGSK3β, Bcl-2, Bax and cleaved caspase-3 proteins. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining and NeuN, and quantified by apoptosis index. Immunohistochemistry and immunofluorescent double-labeling staining was performed to clarify the relationships between neuronal apoptosis and pAkt or pGSK3β.
HS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. The levels of pAkt and pGSK3β, mainly expressed in neurons, were markedly up-regulated. Additionally, Bcl-2 was significantly increased while Bax and cleaved caspase-3 was decreased by HS treatment. Double staining of pAkt and TUNEL showed few colocalization of pAkt-positive cells and TUNEL-positive cells. The inhibitor of PI3K, Ly294002, suppressed the beneficial effects of HS.
HS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway. |
| doi_str_mv | 10.1371/journal.pone.0096212 |
| format | Article |
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Sprague-Dawley rats (n = 85) were randomly divided into the following groups: sham group (n = 17), SAH group (n = 17), SAH + saline group (n = 17), SAH + hydrogen-rich saline (HS) group (n = 17) and SAH + HS + Ly294002 (n = 17) group. HS or an equal volume of physiological saline was administered immediately after surgery and repeated 8 hours later. The PI3K inhibitor, Ly294002, was applied to manipulate the proposed pathway. Neurological score and SAH grade were assessed at 24 hours after SAH. Western blot was used for the quantification of Akt, pAkt, GSK3β, pGSK3β, Bcl-2, Bax and cleaved caspase-3 proteins. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining and NeuN, and quantified by apoptosis index. Immunohistochemistry and immunofluorescent double-labeling staining was performed to clarify the relationships between neuronal apoptosis and pAkt or pGSK3β.
HS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. The levels of pAkt and pGSK3β, mainly expressed in neurons, were markedly up-regulated. Additionally, Bcl-2 was significantly increased while Bax and cleaved caspase-3 was decreased by HS treatment. Double staining of pAkt and TUNEL showed few colocalization of pAkt-positive cells and TUNEL-positive cells. The inhibitor of PI3K, Ly294002, suppressed the beneficial effects of HS.
HS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0096212</identifier><identifier>PMID: 24763696</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Alzheimer's disease ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins - metabolism ; BAX protein ; Bcl-2 protein ; Biology and life sciences ; Brain ; Brain damage ; Brain injury ; Brain research ; Caspase ; Caspase-3 ; Cerebral Cortex - drug effects ; Cerebral Cortex - pathology ; Chromones - pharmacology ; DNA nucleotidylexotransferase ; Enzymes ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; Head injuries ; Hemorrhage ; Hospitals ; Hydrogen ; Immunohistochemistry ; Inhibitors ; Ischemia ; Kinases ; Labelling ; Male ; Medical prognosis ; Medicine ; Medicine and Health Sciences ; Morpholines - pharmacology ; Neurons - drug effects ; Neurons - pathology ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Neurosurgery ; Oxidative stress ; Pathogenesis ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphorylation ; Physiology ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Quality ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rodents ; Signal Transduction ; Signaling ; Sodium Chloride - pharmacology ; Sodium Chloride - therapeutic use ; Spinal cord injuries ; Staining ; Studies ; Subarachnoid hemorrhage ; Subarachnoid Hemorrhage - pathology ; Subarachnoid Hemorrhage - physiopathology ; Subarachnoid Hemorrhage - prevention & control ; Surgery ; Traumatic brain injury ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2014-04, Vol.9 (4), p.e96212</ispartof><rights>2014 Hong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Hong et al 2014 Hong et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-680be86e0d7045359bf4c759f5624de90a862d45640ceb9151534ea73343d7c43</citedby><cites>FETCH-LOGICAL-c526t-680be86e0d7045359bf4c759f5624de90a862d45640ceb9151534ea73343d7c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999200/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999200/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24763696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ai, Jinglu</contributor><creatorcontrib>Hong, Yuan</creatorcontrib><creatorcontrib>Shao, AnWen</creatorcontrib><creatorcontrib>Wang, Jianfeng</creatorcontrib><creatorcontrib>Chen, Sheng</creatorcontrib><creatorcontrib>Wu, HaiJian</creatorcontrib><creatorcontrib>McBride, Devin W</creatorcontrib><creatorcontrib>Wu, Qun</creatorcontrib><creatorcontrib>Sun, XueJun</creatorcontrib><creatorcontrib>Zhang, JianMin</creatorcontrib><title>Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3β signaling pathway</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Neuronal apoptosis is involved in the pathological process of EBI. Hydrogen can inhibit neuronal apoptosis and attenuate EBI following SAH. However, the molecular mechanism underlying hydrogen-mediated anti-apoptotic effects in SAH has not been elucidated. In the present study, we aimed to evaluate whether hydrogen alleviates EBI after SAH, specifically neuronal apoptosis, partially via the Akt/GSK3β signaling pathway.
Sprague-Dawley rats (n = 85) were randomly divided into the following groups: sham group (n = 17), SAH group (n = 17), SAH + saline group (n = 17), SAH + hydrogen-rich saline (HS) group (n = 17) and SAH + HS + Ly294002 (n = 17) group. HS or an equal volume of physiological saline was administered immediately after surgery and repeated 8 hours later. The PI3K inhibitor, Ly294002, was applied to manipulate the proposed pathway. Neurological score and SAH grade were assessed at 24 hours after SAH. Western blot was used for the quantification of Akt, pAkt, GSK3β, pGSK3β, Bcl-2, Bax and cleaved caspase-3 proteins. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining and NeuN, and quantified by apoptosis index. Immunohistochemistry and immunofluorescent double-labeling staining was performed to clarify the relationships between neuronal apoptosis and pAkt or pGSK3β.
HS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. The levels of pAkt and pGSK3β, mainly expressed in neurons, were markedly up-regulated. Additionally, Bcl-2 was significantly increased while Bax and cleaved caspase-3 was decreased by HS treatment. Double staining of pAkt and TUNEL showed few colocalization of pAkt-positive cells and TUNEL-positive cells. The inhibitor of PI3K, Ly294002, suppressed the beneficial effects of HS.
HS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>Biology and life sciences</subject><subject>Brain</subject><subject>Brain damage</subject><subject>Brain injury</subject><subject>Brain research</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cerebral Cortex - drug effects</subject><subject>Cerebral Cortex - pathology</subject><subject>Chromones - pharmacology</subject><subject>DNA nucleotidylexotransferase</subject><subject>Enzymes</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogen Synthase Kinase 3 beta</subject><subject>Head injuries</subject><subject>Hemorrhage</subject><subject>Hospitals</subject><subject>Hydrogen</subject><subject>Immunohistochemistry</subject><subject>Inhibitors</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Labelling</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Morpholines - pharmacology</subject><subject>Neurons - drug effects</subject><subject>Neurons - pathology</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neurosurgery</subject><subject>Oxidative stress</subject><subject>Pathogenesis</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Quality</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Sodium Chloride - pharmacology</subject><subject>Sodium Chloride - therapeutic use</subject><subject>Spinal cord injuries</subject><subject>Staining</subject><subject>Studies</subject><subject>Subarachnoid hemorrhage</subject><subject>Subarachnoid Hemorrhage - pathology</subject><subject>Subarachnoid Hemorrhage - physiopathology</subject><subject>Subarachnoid Hemorrhage - prevention & control</subject><subject>Surgery</subject><subject>Traumatic brain injury</subject><subject>Tumor necrosis factor-TNF</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1ks1u1DAUhSMEou3AGyCwxHqmdvyTmAVSVUGpqGABrC3HuUk8ZOxgO63mtXiDvgDPhIeZVu2Cla_te757dHWK4hXBK0Ircrr2c3B6XE3ewQpjKUpSPimOiaTlUpSYPn1QHxUnMa4x5rQW4nlxVLJKUCHFcXH7Bebgp-ATmGSvAUHX5Qr5Dg3bNvge3DJYM6CoR-sA6V5bFxNyO9noe2tQqze6zz-uRXryU_LRRmQdAh3GLWpCFuTreg5b1Plx9DfW9SjOjQ7aDM7bFg2w8SEMmfIOTT5G24yAMh52NtIA6OxnOr349pn--Y2i7d3OSo8mnYYbvX1RPOv0GOHl4VwUPz5--H7-aXn19eLy_OxqaXgp0lLUuIFaAG4rzDjlsumYqbjsuChZCxLrWpQt44JhA40knHDKQFeUMtpWhtFF8WbPnUYf1WH7UeXGOitF3vWiuNx3tF6v1RTsRoet8tqqfw8-9EqHZM0IijJhakJKAEkZL0ktcUc1b6CtG-CYZNb7w7S52UBrwKWgx0fQxz_ODqr314pKKUuMM-DtARD8rxli-o9ltu8yIe89QHc_gWC1i9mdSu1ipg4xy7LXD93di-5yRf8CzF_WMA</recordid><startdate>20140424</startdate><enddate>20140424</enddate><creator>Hong, Yuan</creator><creator>Shao, AnWen</creator><creator>Wang, Jianfeng</creator><creator>Chen, Sheng</creator><creator>Wu, HaiJian</creator><creator>McBride, Devin W</creator><creator>Wu, Qun</creator><creator>Sun, XueJun</creator><creator>Zhang, JianMin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140424</creationdate><title>Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3β signaling pathway</title><author>Hong, Yuan ; Shao, AnWen ; Wang, Jianfeng ; Chen, Sheng ; Wu, HaiJian ; McBride, Devin W ; Wu, Qun ; Sun, XueJun ; Zhang, JianMin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-680be86e0d7045359bf4c759f5624de90a862d45640ceb9151534ea73343d7c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>BAX protein</topic><topic>Bcl-2 protein</topic><topic>Biology and life sciences</topic><topic>Brain</topic><topic>Brain damage</topic><topic>Brain injury</topic><topic>Brain research</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cerebral Cortex - drug effects</topic><topic>Cerebral Cortex - pathology</topic><topic>Chromones - pharmacology</topic><topic>DNA nucleotidylexotransferase</topic><topic>Enzymes</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogen Synthase Kinase 3 beta</topic><topic>Head injuries</topic><topic>Hemorrhage</topic><topic>Hospitals</topic><topic>Hydrogen</topic><topic>Immunohistochemistry</topic><topic>Inhibitors</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>Labelling</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Morpholines - pharmacology</topic><topic>Neurons - drug effects</topic><topic>Neurons - pathology</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Neurosurgery</topic><topic>Oxidative stress</topic><topic>Pathogenesis</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphorylation</topic><topic>Physiology</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Quality</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Sodium Chloride - pharmacology</topic><topic>Sodium Chloride - therapeutic use</topic><topic>Spinal cord injuries</topic><topic>Staining</topic><topic>Studies</topic><topic>Subarachnoid hemorrhage</topic><topic>Subarachnoid Hemorrhage - pathology</topic><topic>Subarachnoid Hemorrhage - physiopathology</topic><topic>Subarachnoid Hemorrhage - prevention & control</topic><topic>Surgery</topic><topic>Traumatic brain injury</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hong, Yuan</creatorcontrib><creatorcontrib>Shao, AnWen</creatorcontrib><creatorcontrib>Wang, Jianfeng</creatorcontrib><creatorcontrib>Chen, Sheng</creatorcontrib><creatorcontrib>Wu, HaiJian</creatorcontrib><creatorcontrib>McBride, Devin W</creatorcontrib><creatorcontrib>Wu, Qun</creatorcontrib><creatorcontrib>Sun, XueJun</creatorcontrib><creatorcontrib>Zhang, JianMin</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hong, Yuan</au><au>Shao, AnWen</au><au>Wang, Jianfeng</au><au>Chen, Sheng</au><au>Wu, HaiJian</au><au>McBride, Devin W</au><au>Wu, Qun</au><au>Sun, XueJun</au><au>Zhang, JianMin</au><au>Ai, Jinglu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3β signaling pathway</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-04-24</date><risdate>2014</risdate><volume>9</volume><issue>4</issue><spage>e96212</spage><pages>e96212-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Neuronal apoptosis is involved in the pathological process of EBI. Hydrogen can inhibit neuronal apoptosis and attenuate EBI following SAH. However, the molecular mechanism underlying hydrogen-mediated anti-apoptotic effects in SAH has not been elucidated. In the present study, we aimed to evaluate whether hydrogen alleviates EBI after SAH, specifically neuronal apoptosis, partially via the Akt/GSK3β signaling pathway.
Sprague-Dawley rats (n = 85) were randomly divided into the following groups: sham group (n = 17), SAH group (n = 17), SAH + saline group (n = 17), SAH + hydrogen-rich saline (HS) group (n = 17) and SAH + HS + Ly294002 (n = 17) group. HS or an equal volume of physiological saline was administered immediately after surgery and repeated 8 hours later. The PI3K inhibitor, Ly294002, was applied to manipulate the proposed pathway. Neurological score and SAH grade were assessed at 24 hours after SAH. Western blot was used for the quantification of Akt, pAkt, GSK3β, pGSK3β, Bcl-2, Bax and cleaved caspase-3 proteins. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining and NeuN, and quantified by apoptosis index. Immunohistochemistry and immunofluorescent double-labeling staining was performed to clarify the relationships between neuronal apoptosis and pAkt or pGSK3β.
HS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. The levels of pAkt and pGSK3β, mainly expressed in neurons, were markedly up-regulated. Additionally, Bcl-2 was significantly increased while Bax and cleaved caspase-3 was decreased by HS treatment. Double staining of pAkt and TUNEL showed few colocalization of pAkt-positive cells and TUNEL-positive cells. The inhibitor of PI3K, Ly294002, suppressed the beneficial effects of HS.
HS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24763696</pmid><doi>10.1371/journal.pone.0096212</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-04, Vol.9 (4), p.e96212 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1518862619 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Alzheimer's disease Animals Apoptosis Apoptosis - drug effects Apoptosis Regulatory Proteins - metabolism BAX protein Bcl-2 protein Biology and life sciences Brain Brain damage Brain injury Brain research Caspase Caspase-3 Cerebral Cortex - drug effects Cerebral Cortex - pathology Chromones - pharmacology DNA nucleotidylexotransferase Enzymes Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 beta Head injuries Hemorrhage Hospitals Hydrogen Immunohistochemistry Inhibitors Ischemia Kinases Labelling Male Medical prognosis Medicine Medicine and Health Sciences Morpholines - pharmacology Neurons - drug effects Neurons - pathology Neuroprotection Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Neurosurgery Oxidative stress Pathogenesis Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphorylation Physiology Proteins Proto-Oncogene Proteins c-akt - metabolism Quality Random Allocation Rats Rats, Sprague-Dawley Rodents Signal Transduction Signaling Sodium Chloride - pharmacology Sodium Chloride - therapeutic use Spinal cord injuries Staining Studies Subarachnoid hemorrhage Subarachnoid Hemorrhage - pathology Subarachnoid Hemorrhage - physiopathology Subarachnoid Hemorrhage - prevention & control Surgery Traumatic brain injury Tumor necrosis factor-TNF |
| title | Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3β signaling pathway |
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