The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model
BACKGROUND Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study availa...
Gespeichert in:
| Veröffentlicht in: | Medical science monitor 2016-12, Vol.22, p.5074-5081 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5081 |
|---|---|
| container_issue | |
| container_start_page | 5074 |
| container_title | Medical science monitor |
| container_volume | 22 |
| creator | Xiao, Jinglei Tan, Yongchang Li, Yinjiao Luo, Yan |
| description | BACKGROUND Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. MATERIAL AND METHODS Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia. Western blot analysis was performed to quantify the phosphorylation of the PKR at 0 h, 3 h, 6 h, 12 h, 24 h, and phosphorylation of NF-κB 24h after hypoxia exposure. The TTC stain for infarction area and TUNEL stain for apoptotic cells were assayed 24 h after the brain hypoxia. Gene expression of IL-1β, IL-6, and TNF-α was performed at 3 h, 6 h, 12 h, and 24 h. RESULTS The level of PKR autophosphorylation was increased dramatically, especially at 3 h (C16 group vs. HI group, P |
| doi_str_mv | 10.12659/MSM.898139 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5207129</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1852784480</sourcerecordid><originalsourceid>FETCH-LOGICAL-c423t-4462d727227c828bd94577c9e5b0ff40a48ec44f2f977dbc9ea1a6893ccd5ea33</originalsourceid><addsrcrecordid>eNpVkU1v1DAQhi0Eoh9w4o58LKpSbMeJnQtSWT66aheqbTlbE2eya5TYi-1F7F_h1xKxbSmnGWmeeWakl5BXnJ1xUVfN28XN4kw3mpfNE3LIa1kWparY00f9ATlK6TtjQtesek4OhGZM60Yekt-3a6Q3G7Sud5Zex5DReXrpPCSkS3pyfbl8Q-d-7VqXQ6QzXu8hmxP9gsFDhoFe7Dbhl4NinuwaRwf0fYTJ8gFGWGGi7e7e4Pxq2trG4Hw_wDhCdsHTCYV_siVkuggdDi_Isx6GhC_v6jH59unj7eyiuPr6eT47vyqsFGUupKxFp4QSQlktdNs1slLKNli1rO8lA6nRStmLvlGqa6cBcKh1U1rbVQhleUze7b2bbTtiZ9HnCIPZRDdC3JkAzvw_8W5tVuGnqQRTXDST4OROEMOPLaZsRpcsDgN4DNtkuK6E0lJqNqGne9TGkFLE_uEMZ-ZvmmZK0-zTnOjXjz97YO_jK_8AGbicaQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1852784480</pqid></control><display><type>article</type><title>The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model</title><source>Electronic Journals Library</source><source>Open Access: PubMed Central</source><source>MEDLINE</source><source>PubMed Central Open Access</source><creator>Xiao, Jinglei ; Tan, Yongchang ; Li, Yinjiao ; Luo, Yan</creator><creatorcontrib>Xiao, Jinglei ; Tan, Yongchang ; Li, Yinjiao ; Luo, Yan</creatorcontrib><description>BACKGROUND Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. MATERIAL AND METHODS Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia. Western blot analysis was performed to quantify the phosphorylation of the PKR at 0 h, 3 h, 6 h, 12 h, 24 h, and phosphorylation of NF-κB 24h after hypoxia exposure. The TTC stain for infarction area and TUNEL stain for apoptotic cells were assayed 24 h after the brain hypoxia. Gene expression of IL-1β, IL-6, and TNF-α was performed at 3 h, 6 h, 12 h, and 24 h. RESULTS The level of PKR autophosphorylation was increased dramatically, especially at 3 h (C16 group vs. HI group, P<0.01). Intraperitoneal C16 administration reduced the infarct volume and apoptosis ratio after this insult (C16 group vs. HI group<0.01), and C16 reduced proinflammatory cytokines mRNA expression, partly through inhibiting NF-κB activation (C16 group vs. HI group<0.05). CONCLUSIONS C16 can protect immature rats against hypoxia-ischemia-induced brain damage by modulating neuroinflammation.</description><identifier>ISSN: 1643-3750</identifier><identifier>ISSN: 1234-1010</identifier><identifier>EISSN: 1643-3750</identifier><identifier>DOI: 10.12659/MSM.898139</identifier><identifier>PMID: 28008894</identifier><language>eng</language><publisher>United States: International Scientific Literature, Inc</publisher><subject><![CDATA[Animal Study ; Animals ; Animals, Newborn ; Apoptosis - drug effects ; Brain ; Cytokines - genetics ; Cytokines - metabolism ; Disease Models, Animal ; eIF-2 Kinase - antagonists & inhibitors ; eIF-2 Kinase - metabolism ; Hypoxia-Ischemia, Brain - complications ; Hypoxia-Ischemia, Brain - pathology ; Hypoxia-Ischemia, Brain - prevention & control ; Indoles - administration & dosage ; Indoles - pharmacology ; Indoles - therapeutic use ; Inflammation - complications ; Inflammation - drug therapy ; Inflammation - pathology ; Injections, Intraperitoneal ; Male ; Neurons - drug effects ; Neurons - pathology ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; NF-kappa B - metabolism ; Phosphorylation - drug effects ; Protein Kinase Inhibitors - administration & dosage ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Rats, Sprague-Dawley ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Thiazoles - administration & dosage ; Thiazoles - pharmacology ; Thiazoles - therapeutic use]]></subject><ispartof>Medical science monitor, 2016-12, Vol.22, p.5074-5081</ispartof><rights>Med Sci Monit, 2016 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-4462d727227c828bd94577c9e5b0ff40a48ec44f2f977dbc9ea1a6893ccd5ea33</citedby><cites>FETCH-LOGICAL-c423t-4462d727227c828bd94577c9e5b0ff40a48ec44f2f977dbc9ea1a6893ccd5ea33</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/PMC5207129/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207129/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28008894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiao, Jinglei</creatorcontrib><creatorcontrib>Tan, Yongchang</creatorcontrib><creatorcontrib>Li, Yinjiao</creatorcontrib><creatorcontrib>Luo, Yan</creatorcontrib><title>The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model</title><title>Medical science monitor</title><addtitle>Med Sci Monit</addtitle><description>BACKGROUND Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. MATERIAL AND METHODS Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia. Western blot analysis was performed to quantify the phosphorylation of the PKR at 0 h, 3 h, 6 h, 12 h, 24 h, and phosphorylation of NF-κB 24h after hypoxia exposure. The TTC stain for infarction area and TUNEL stain for apoptotic cells were assayed 24 h after the brain hypoxia. Gene expression of IL-1β, IL-6, and TNF-α was performed at 3 h, 6 h, 12 h, and 24 h. RESULTS The level of PKR autophosphorylation was increased dramatically, especially at 3 h (C16 group vs. HI group, P<0.01). Intraperitoneal C16 administration reduced the infarct volume and apoptosis ratio after this insult (C16 group vs. HI group<0.01), and C16 reduced proinflammatory cytokines mRNA expression, partly through inhibiting NF-κB activation (C16 group vs. HI group<0.05). CONCLUSIONS C16 can protect immature rats against hypoxia-ischemia-induced brain damage by modulating neuroinflammation.</description><subject>Animal Study</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Apoptosis - drug effects</subject><subject>Brain</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>eIF-2 Kinase - antagonists & inhibitors</subject><subject>eIF-2 Kinase - metabolism</subject><subject>Hypoxia-Ischemia, Brain - complications</subject><subject>Hypoxia-Ischemia, Brain - pathology</subject><subject>Hypoxia-Ischemia, Brain - prevention & control</subject><subject>Indoles - administration & dosage</subject><subject>Indoles - pharmacology</subject><subject>Indoles - therapeutic use</subject><subject>Inflammation - complications</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - pathology</subject><subject>Injections, Intraperitoneal</subject><subject>Male</subject><subject>Neurons - drug effects</subject><subject>Neurons - pathology</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>NF-kappa B - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Kinase Inhibitors - administration & dosage</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Thiazoles - administration & dosage</subject><subject>Thiazoles - pharmacology</subject><subject>Thiazoles - therapeutic use</subject><issn>1643-3750</issn><issn>1234-1010</issn><issn>1643-3750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1v1DAQhi0Eoh9w4o58LKpSbMeJnQtSWT66aheqbTlbE2eya5TYi-1F7F_h1xKxbSmnGWmeeWakl5BXnJ1xUVfN28XN4kw3mpfNE3LIa1kWparY00f9ATlK6TtjQtesek4OhGZM60Yekt-3a6Q3G7Sud5Zex5DReXrpPCSkS3pyfbl8Q-d-7VqXQ6QzXu8hmxP9gsFDhoFe7Dbhl4NinuwaRwf0fYTJ8gFGWGGi7e7e4Pxq2trG4Hw_wDhCdsHTCYV_siVkuggdDi_Isx6GhC_v6jH59unj7eyiuPr6eT47vyqsFGUupKxFp4QSQlktdNs1slLKNli1rO8lA6nRStmLvlGqa6cBcKh1U1rbVQhleUze7b2bbTtiZ9HnCIPZRDdC3JkAzvw_8W5tVuGnqQRTXDST4OROEMOPLaZsRpcsDgN4DNtkuK6E0lJqNqGne9TGkFLE_uEMZ-ZvmmZK0-zTnOjXjz97YO_jK_8AGbicaQ</recordid><startdate>20161223</startdate><enddate>20161223</enddate><creator>Xiao, Jinglei</creator><creator>Tan, Yongchang</creator><creator>Li, Yinjiao</creator><creator>Luo, Yan</creator><general>International Scientific Literature, 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><scope>5PM</scope></search><sort><creationdate>20161223</creationdate><title>The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model</title><author>Xiao, Jinglei ; Tan, Yongchang ; Li, Yinjiao ; Luo, Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-4462d727227c828bd94577c9e5b0ff40a48ec44f2f977dbc9ea1a6893ccd5ea33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animal Study</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Apoptosis - drug effects</topic><topic>Brain</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>eIF-2 Kinase - antagonists & inhibitors</topic><topic>eIF-2 Kinase - metabolism</topic><topic>Hypoxia-Ischemia, Brain - complications</topic><topic>Hypoxia-Ischemia, Brain - pathology</topic><topic>Hypoxia-Ischemia, Brain - prevention & control</topic><topic>Indoles - administration & dosage</topic><topic>Indoles - pharmacology</topic><topic>Indoles - therapeutic use</topic><topic>Inflammation - complications</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - pathology</topic><topic>Injections, Intraperitoneal</topic><topic>Male</topic><topic>Neurons - drug effects</topic><topic>Neurons - pathology</topic><topic>Neuroprotective Agents - administration & dosage</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>NF-kappa B - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Kinase Inhibitors - administration & dosage</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Thiazoles - administration & dosage</topic><topic>Thiazoles - pharmacology</topic><topic>Thiazoles - therapeutic use</topic><toplevel>online_resources</toplevel><creatorcontrib>Xiao, Jinglei</creatorcontrib><creatorcontrib>Tan, Yongchang</creatorcontrib><creatorcontrib>Li, Yinjiao</creatorcontrib><creatorcontrib>Luo, Yan</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medical science monitor</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiao, Jinglei</au><au>Tan, Yongchang</au><au>Li, Yinjiao</au><au>Luo, Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model</atitle><jtitle>Medical science monitor</jtitle><addtitle>Med Sci Monit</addtitle><date>2016-12-23</date><risdate>2016</risdate><volume>22</volume><spage>5074</spage><epage>5081</epage><pages>5074-5081</pages><issn>1643-3750</issn><issn>1234-1010</issn><eissn>1643-3750</eissn><abstract>BACKGROUND Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. MATERIAL AND METHODS Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia. Western blot analysis was performed to quantify the phosphorylation of the PKR at 0 h, 3 h, 6 h, 12 h, 24 h, and phosphorylation of NF-κB 24h after hypoxia exposure. The TTC stain for infarction area and TUNEL stain for apoptotic cells were assayed 24 h after the brain hypoxia. Gene expression of IL-1β, IL-6, and TNF-α was performed at 3 h, 6 h, 12 h, and 24 h. RESULTS The level of PKR autophosphorylation was increased dramatically, especially at 3 h (C16 group vs. HI group, P<0.01). Intraperitoneal C16 administration reduced the infarct volume and apoptosis ratio after this insult (C16 group vs. HI group<0.01), and C16 reduced proinflammatory cytokines mRNA expression, partly through inhibiting NF-κB activation (C16 group vs. HI group<0.05). CONCLUSIONS C16 can protect immature rats against hypoxia-ischemia-induced brain damage by modulating neuroinflammation.</abstract><cop>United States</cop><pub>International Scientific Literature, Inc</pub><pmid>28008894</pmid><doi>10.12659/MSM.898139</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1643-3750 |
| ispartof | Medical science monitor, 2016-12, Vol.22, p.5074-5081 |
| issn | 1643-3750 1234-1010 1643-3750 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5207129 |
| source | Electronic Journals Library; Open Access: PubMed Central; MEDLINE; PubMed Central Open Access |
| subjects | Animal Study Animals Animals, Newborn Apoptosis - drug effects Brain Cytokines - genetics Cytokines - metabolism Disease Models, Animal eIF-2 Kinase - antagonists & inhibitors eIF-2 Kinase - metabolism Hypoxia-Ischemia, Brain - complications Hypoxia-Ischemia, Brain - pathology Hypoxia-Ischemia, Brain - prevention & control Indoles - administration & dosage Indoles - pharmacology Indoles - therapeutic use Inflammation - complications Inflammation - drug therapy Inflammation - pathology Injections, Intraperitoneal Male Neurons - drug effects Neurons - pathology Neuroprotective Agents - administration & dosage Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use NF-kappa B - metabolism Phosphorylation - drug effects Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Rats, Sprague-Dawley RNA, Messenger - genetics RNA, Messenger - metabolism Thiazoles - administration & dosage Thiazoles - pharmacology Thiazoles - therapeutic use |
| title | The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T11%3A06%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Specific%20Protein%20Kinase%20R%20(PKR)%20Inhibitor%20C16%20Protects%20Neonatal%20Hypoxia-Ischemia%20Brain%20Damages%20by%20Inhibiting%20Neuroinflammation%20in%20a%20Neonatal%20Rat%20Model&rft.jtitle=Medical%20science%20monitor&rft.au=Xiao,%20Jinglei&rft.date=2016-12-23&rft.volume=22&rft.spage=5074&rft.epage=5081&rft.pages=5074-5081&rft.issn=1643-3750&rft.eissn=1643-3750&rft_id=info:doi/10.12659/MSM.898139&rft_dat=%3Cproquest_pubme%3E1852784480%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1852784480&rft_id=info:pmid/28008894&rfr_iscdi=true |