Resveratrol prevents neuronal apoptosis in an early brain injury model
Abstract Background Resveratrol has been shown to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH); however, no study has explored its neuroprotective effect in early brain injury (EBI) after experimental SAH. The aim of this study was to evaluate the antiapoptotic function of resver...
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creator | Zhou, Xiao-Ming, MD Zhou, Meng-Liang, MD, PhD Zhang, Xiang-Sheng, MD Zhuang, Zong, MD, PhD Li, Tao, MD Shi, Ji-Xin, MD, PhD Zhang, Xin, MD, PhD |
description | Abstract Background Resveratrol has been shown to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH); however, no study has explored its neuroprotective effect in early brain injury (EBI) after experimental SAH. The aim of this study was to evaluate the antiapoptotic function of resveratrol in EBI and its relationship with the PI3K/Akt survival pathway. Methods Experimental SAH was induced in adult male rats by prechiasmatic cistern injection. Control and SAH rats were divided into six groups and treated with low (20 mg/kg) or high (60 mg/kg) concentrations of resveratrol with or without LY294002 cotreatment. Brain samples of the rats were analyzed by immunohistochemistry, immunofluorescence staining, Western blotting, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assays. Results High-concentration but not low-concentration resveratrol treatment in SAH rats led to a significant increase in phosphorylated Akt (p-Akt) protein levels compared with SAH rats without treatment. In addition, p-Akt–positive cells mainly colocalized with NeuN-positive cells. Neuronal apoptosis in SAH rat brain was attenuated by high-concentration resveratrol treatment. The antiapoptotic effect of resveratrol in SAH rats could be partially abrogated by the PI3K/Akt signaling inhibitor LY294002. Conclusions Our results show that resveratrol has an antiapoptotic effect in EBI and that resveratrol might act through the PI3K/Akt signaling pathway. |
doi_str_mv | 10.1016/j.jss.2014.01.062 |
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The aim of this study was to evaluate the antiapoptotic function of resveratrol in EBI and its relationship with the PI3K/Akt survival pathway. Methods Experimental SAH was induced in adult male rats by prechiasmatic cistern injection. Control and SAH rats were divided into six groups and treated with low (20 mg/kg) or high (60 mg/kg) concentrations of resveratrol with or without LY294002 cotreatment. Brain samples of the rats were analyzed by immunohistochemistry, immunofluorescence staining, Western blotting, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assays. Results High-concentration but not low-concentration resveratrol treatment in SAH rats led to a significant increase in phosphorylated Akt (p-Akt) protein levels compared with SAH rats without treatment. In addition, p-Akt–positive cells mainly colocalized with NeuN-positive cells. Neuronal apoptosis in SAH rat brain was attenuated by high-concentration resveratrol treatment. The antiapoptotic effect of resveratrol in SAH rats could be partially abrogated by the PI3K/Akt signaling inhibitor LY294002. Conclusions Our results show that resveratrol has an antiapoptotic effect in EBI and that resveratrol might act through the PI3K/Akt signaling pathway.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2014.01.062</identifier><identifier>PMID: 24602480</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Akt ; Animals ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; Apoptosis ; Apoptosis - drug effects ; Brain Injuries - drug therapy ; Brain Injuries - pathology ; Disease Models, Animal ; Early brain injury ; Early Diagnosis ; Interneurons - drug effects ; Interneurons - metabolism ; Interneurons - pathology ; Male ; Phosphatidylinositol 3-Kinases - metabolism ; Phytotherapy ; PI3K ; Plant Extracts - pharmacology ; Plant Extracts - therapeutic use ; Proto-Oncogene Proteins c-akt - metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Resveratrol ; Stilbenes - pharmacology ; Stilbenes - therapeutic use ; Subarachnoid hemorrhage ; Subarachnoid Hemorrhage - drug therapy ; Subarachnoid Hemorrhage - metabolism ; Subarachnoid Hemorrhage - pathology ; Surgery</subject><ispartof>The Journal of surgical research, 2014-06, Vol.189 (1), p.159-165</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-31b8eeea3972c3cc1235da8864bb909899b7fa86a51fb2213b5c556bed9ac5a83</citedby><cites>FETCH-LOGICAL-c408t-31b8eeea3972c3cc1235da8864bb909899b7fa86a51fb2213b5c556bed9ac5a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jss.2014.01.062$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24602480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Xiao-Ming, MD</creatorcontrib><creatorcontrib>Zhou, Meng-Liang, MD, PhD</creatorcontrib><creatorcontrib>Zhang, Xiang-Sheng, MD</creatorcontrib><creatorcontrib>Zhuang, Zong, MD, PhD</creatorcontrib><creatorcontrib>Li, Tao, MD</creatorcontrib><creatorcontrib>Shi, Ji-Xin, MD, PhD</creatorcontrib><creatorcontrib>Zhang, Xin, MD, PhD</creatorcontrib><title>Resveratrol prevents neuronal apoptosis in an early brain injury model</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Abstract Background Resveratrol has been shown to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH); however, no study has explored its neuroprotective effect in early brain injury (EBI) after experimental SAH. The aim of this study was to evaluate the antiapoptotic function of resveratrol in EBI and its relationship with the PI3K/Akt survival pathway. Methods Experimental SAH was induced in adult male rats by prechiasmatic cistern injection. Control and SAH rats were divided into six groups and treated with low (20 mg/kg) or high (60 mg/kg) concentrations of resveratrol with or without LY294002 cotreatment. Brain samples of the rats were analyzed by immunohistochemistry, immunofluorescence staining, Western blotting, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assays. Results High-concentration but not low-concentration resveratrol treatment in SAH rats led to a significant increase in phosphorylated Akt (p-Akt) protein levels compared with SAH rats without treatment. In addition, p-Akt–positive cells mainly colocalized with NeuN-positive cells. Neuronal apoptosis in SAH rat brain was attenuated by high-concentration resveratrol treatment. The antiapoptotic effect of resveratrol in SAH rats could be partially abrogated by the PI3K/Akt signaling inhibitor LY294002. Conclusions Our results show that resveratrol has an antiapoptotic effect in EBI and that resveratrol might act through the PI3K/Akt signaling pathway.</description><subject>Akt</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Brain Injuries - drug therapy</subject><subject>Brain Injuries - pathology</subject><subject>Disease Models, Animal</subject><subject>Early brain injury</subject><subject>Early Diagnosis</subject><subject>Interneurons - drug effects</subject><subject>Interneurons - metabolism</subject><subject>Interneurons - pathology</subject><subject>Male</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phytotherapy</subject><subject>PI3K</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Extracts - therapeutic use</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Resveratrol</subject><subject>Stilbenes - pharmacology</subject><subject>Stilbenes - therapeutic use</subject><subject>Subarachnoid hemorrhage</subject><subject>Subarachnoid Hemorrhage - drug therapy</subject><subject>Subarachnoid Hemorrhage - metabolism</subject><subject>Subarachnoid Hemorrhage - pathology</subject><subject>Surgery</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFr3DAQhUVpaTZpf0Avwcde7Iwky5YJBEpomkCgkLRnIcmzIFcrOZK9sP--WjbtoYeehmHee_C-IeQThYYC7a6mZsq5YUDbBmgDHXtDNhQGUcuu52_JBoCxupXQnpHznCco-9Dz9-SMtR2wctiQuyfMe0x6SdFXc8I9hiVXAdcUg_aVnuO8xOxy5UKlQ4U6-UNlki6rC9OaDtUujug_kHdb7TN-fJ0X5Ofd1x-39_Xj928Pt18ea9uCXGpOjUREzYeeWW4tZVyMWsquNWaAQQ6D6bdadlrQrWGMciOsEJ3BcdBWaMkvyOdT7pziy4p5UTuXLXqvA8Y1KyqoLOX6DoqUnqQ2xZwTbtWc3E6ng6KgjvjUpAo-dcSngKqCr3guX-NXs8Pxr-MPryK4PgmwlNw7TCpbh8Hi6BLaRY3R_Tf-5h-39S44q_0vPGCe4poK9NJCZaZAPR__d3wfbQEoSMF_A56VlXU</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Zhou, Xiao-Ming, MD</creator><creator>Zhou, Meng-Liang, MD, PhD</creator><creator>Zhang, Xiang-Sheng, MD</creator><creator>Zhuang, Zong, MD, PhD</creator><creator>Li, Tao, MD</creator><creator>Shi, Ji-Xin, MD, PhD</creator><creator>Zhang, Xin, MD, PhD</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20140601</creationdate><title>Resveratrol prevents neuronal apoptosis in an early brain injury model</title><author>Zhou, Xiao-Ming, MD ; Zhou, Meng-Liang, MD, PhD ; Zhang, Xiang-Sheng, MD ; Zhuang, Zong, MD, PhD ; Li, Tao, MD ; Shi, Ji-Xin, MD, PhD ; Zhang, Xin, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-31b8eeea3972c3cc1235da8864bb909899b7fa86a51fb2213b5c556bed9ac5a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Akt</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Brain Injuries - drug therapy</topic><topic>Brain Injuries - pathology</topic><topic>Disease Models, Animal</topic><topic>Early brain injury</topic><topic>Early Diagnosis</topic><topic>Interneurons - drug effects</topic><topic>Interneurons - metabolism</topic><topic>Interneurons - pathology</topic><topic>Male</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phytotherapy</topic><topic>PI3K</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Extracts - therapeutic use</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Resveratrol</topic><topic>Stilbenes - pharmacology</topic><topic>Stilbenes - therapeutic use</topic><topic>Subarachnoid hemorrhage</topic><topic>Subarachnoid Hemorrhage - drug therapy</topic><topic>Subarachnoid Hemorrhage - metabolism</topic><topic>Subarachnoid Hemorrhage - pathology</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Xiao-Ming, MD</creatorcontrib><creatorcontrib>Zhou, Meng-Liang, MD, PhD</creatorcontrib><creatorcontrib>Zhang, Xiang-Sheng, MD</creatorcontrib><creatorcontrib>Zhuang, Zong, MD, PhD</creatorcontrib><creatorcontrib>Li, Tao, MD</creatorcontrib><creatorcontrib>Shi, Ji-Xin, MD, PhD</creatorcontrib><creatorcontrib>Zhang, Xin, MD, PhD</creatorcontrib><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><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Xiao-Ming, MD</au><au>Zhou, Meng-Liang, MD, PhD</au><au>Zhang, Xiang-Sheng, MD</au><au>Zhuang, Zong, MD, PhD</au><au>Li, Tao, MD</au><au>Shi, Ji-Xin, MD, PhD</au><au>Zhang, Xin, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resveratrol prevents neuronal apoptosis in an early brain injury model</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>189</volume><issue>1</issue><spage>159</spage><epage>165</epage><pages>159-165</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Abstract Background Resveratrol has been shown to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH); however, no study has explored its neuroprotective effect in early brain injury (EBI) after experimental SAH. The aim of this study was to evaluate the antiapoptotic function of resveratrol in EBI and its relationship with the PI3K/Akt survival pathway. Methods Experimental SAH was induced in adult male rats by prechiasmatic cistern injection. Control and SAH rats were divided into six groups and treated with low (20 mg/kg) or high (60 mg/kg) concentrations of resveratrol with or without LY294002 cotreatment. Brain samples of the rats were analyzed by immunohistochemistry, immunofluorescence staining, Western blotting, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assays. Results High-concentration but not low-concentration resveratrol treatment in SAH rats led to a significant increase in phosphorylated Akt (p-Akt) protein levels compared with SAH rats without treatment. In addition, p-Akt–positive cells mainly colocalized with NeuN-positive cells. Neuronal apoptosis in SAH rat brain was attenuated by high-concentration resveratrol treatment. The antiapoptotic effect of resveratrol in SAH rats could be partially abrogated by the PI3K/Akt signaling inhibitor LY294002. Conclusions Our results show that resveratrol has an antiapoptotic effect in EBI and that resveratrol might act through the PI3K/Akt signaling pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24602480</pmid><doi>10.1016/j.jss.2014.01.062</doi><tpages>7</tpages></addata></record> |
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subjects | Akt Animals Antioxidants - pharmacology Antioxidants - therapeutic use Apoptosis Apoptosis - drug effects Brain Injuries - drug therapy Brain Injuries - pathology Disease Models, Animal Early brain injury Early Diagnosis Interneurons - drug effects Interneurons - metabolism Interneurons - pathology Male Phosphatidylinositol 3-Kinases - metabolism Phytotherapy PI3K Plant Extracts - pharmacology Plant Extracts - therapeutic use Proto-Oncogene Proteins c-akt - metabolism Random Allocation Rats Rats, Sprague-Dawley Resveratrol Stilbenes - pharmacology Stilbenes - therapeutic use Subarachnoid hemorrhage Subarachnoid Hemorrhage - drug therapy Subarachnoid Hemorrhage - metabolism Subarachnoid Hemorrhage - pathology Surgery |
title | Resveratrol prevents neuronal apoptosis in an early brain injury model |
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