Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats
A recent study has shown that increased activity of matrix metalloproteinases‐2 and metalloproteinases‐9 (MMP‐2 and MMP‐9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP‐2 and M...
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| Veröffentlicht in: | Developmental neurobiology (Hoboken, N.J.) N.J.), 2010-02, Vol.70 (3), p.182-194 |
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| creator | Tong, Wenni Chen, Wanqiu Ostrowski, Robert P. Ma, Qingyi Souvenir, Rhonda Zhang, Lubo Zhang, John H. Tang, Jiping |
| description | A recent study has shown that increased activity of matrix metalloproteinases‐2 and metalloproteinases‐9 (MMP‐2 and MMP‐9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP‐2 and MMP‐9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP‐1 and TIMP‐2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP‐2 and MMP‐9 and the protein abundance of TIMP‐1 and TIMP‐2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP‐2 at day 0, and increased MMP‐9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP‐2, MMP‐9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010 |
| doi_str_mv | 10.1002/dneu.20770 |
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The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP‐2 and MMP‐9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP‐1 and TIMP‐2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP‐2 and MMP‐9 and the protein abundance of TIMP‐1 and TIMP‐2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP‐2 at day 0, and increased MMP‐9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP‐2, MMP‐9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010</description><identifier>ISSN: 1932-8451</identifier><identifier>EISSN: 1932-846X</identifier><identifier>DOI: 10.1002/dneu.20770</identifier><identifier>PMID: 20017119</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Animals, Newborn ; Brain - growth & development ; Brain - metabolism ; Cell Death ; chronic hypoxia ; development ; Female ; Hippocampus - growth & development ; Hippocampus - metabolism ; Hypoxia - complications ; maternal ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; matrix metalloproteinases ; Matrix Metalloproteinases - metabolism ; neonate ; Neurons - metabolism ; Neuropsychological Tests ; Pregnancy ; Pregnancy Complications ; Prenatal Exposure Delayed Effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 - metabolism ; Tissue Inhibitor of Metalloproteinase-2 - metabolism ; Tissue Inhibitor of Metalloproteinases - metabolism</subject><ispartof>Developmental neurobiology (Hoboken, N.J.), 2010-02, Vol.70 (3), p.182-194</ispartof><rights>Copyright © 2009 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4510-98dcf9e22d161ef95a440a6562e876dee149906562a4bd68c80e143eb52fd2153</citedby><cites>FETCH-LOGICAL-c4510-98dcf9e22d161ef95a440a6562e876dee149906562a4bd68c80e143eb52fd2153</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdneu.20770$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdneu.20770$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1416,1432,27922,27923,45572,45573,46407,46831</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20017119$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tong, Wenni</creatorcontrib><creatorcontrib>Chen, Wanqiu</creatorcontrib><creatorcontrib>Ostrowski, Robert P.</creatorcontrib><creatorcontrib>Ma, Qingyi</creatorcontrib><creatorcontrib>Souvenir, Rhonda</creatorcontrib><creatorcontrib>Zhang, Lubo</creatorcontrib><creatorcontrib>Zhang, John H.</creatorcontrib><creatorcontrib>Tang, Jiping</creatorcontrib><title>Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats</title><title>Developmental neurobiology (Hoboken, N.J.)</title><addtitle>Dev Neurobiol</addtitle><description>A recent study has shown that increased activity of matrix metalloproteinases‐2 and metalloproteinases‐9 (MMP‐2 and MMP‐9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP‐2 and MMP‐9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP‐1 and TIMP‐2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP‐2 and MMP‐9 and the protein abundance of TIMP‐1 and TIMP‐2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP‐2 at day 0, and increased MMP‐9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP‐2, MMP‐9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Brain - growth & development</subject><subject>Brain - metabolism</subject><subject>Cell Death</subject><subject>chronic hypoxia</subject><subject>development</subject><subject>Female</subject><subject>Hippocampus - growth & development</subject><subject>Hippocampus - metabolism</subject><subject>Hypoxia - complications</subject><subject>maternal</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>matrix metalloproteinases</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>neonate</subject><subject>Neurons - metabolism</subject><subject>Neuropsychological Tests</subject><subject>Pregnancy</subject><subject>Pregnancy Complications</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinase-2 - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><issn>1932-8451</issn><issn>1932-846X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1LAzEQhoMoflQv_gDZmyC0Jtmv5CJI_SpY9aDgLcxuZm1km63Jrrb_3t1Wi170lGTm4ckMLyGHjA4YpfxUW2wGnKYp3SC7TIa8L6LkeXN9j9kO2fP-ldI45AndJjucUpYyJneJH0ONzkIZTBazam4gMDZ3CB59UE8wgLw276ZeBFURjMcPPgCrA40_EZzPHHpvKttBj6OOMnbZyhyYZdViZaFuf3FQ-32yVUDp8eDr7JGnq8vH4U3_9v56NDy_7eftyLQvhc4LiZxrljAsZAxRRCGJE44iTTQii6Sk3RuiTCciF7QthZjFvNCcxWGPnK28syabos7R1g5KNXNmCm6hKjDqd8eaiXqp3hUXTEZUtILjL4Gr3hr0tZoan2NZQrtP41UaxUnEBJf_k2EYC5amaUuerMjcVd47LNbzMKq6OFUXp1rG2cJHPzdYo9_5tQBbAR-mxMUfKnVxd_m0kn4CGd-sCg</recordid><startdate>20100215</startdate><enddate>20100215</enddate><creator>Tong, Wenni</creator><creator>Chen, Wanqiu</creator><creator>Ostrowski, Robert P.</creator><creator>Ma, Qingyi</creator><creator>Souvenir, Rhonda</creator><creator>Zhang, Lubo</creator><creator>Zhang, John H.</creator><creator>Tang, Jiping</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>7TK</scope><scope>5PM</scope></search><sort><creationdate>20100215</creationdate><title>Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats</title><author>Tong, Wenni ; Chen, Wanqiu ; Ostrowski, Robert P. ; Ma, Qingyi ; Souvenir, Rhonda ; Zhang, Lubo ; Zhang, John H. ; Tang, Jiping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4510-98dcf9e22d161ef95a440a6562e876dee149906562a4bd68c80e143eb52fd2153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Brain - growth & development</topic><topic>Brain - metabolism</topic><topic>Cell Death</topic><topic>chronic hypoxia</topic><topic>development</topic><topic>Female</topic><topic>Hippocampus - growth & development</topic><topic>Hippocampus - metabolism</topic><topic>Hypoxia - complications</topic><topic>maternal</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>matrix metalloproteinases</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>neonate</topic><topic>Neurons - metabolism</topic><topic>Neuropsychological Tests</topic><topic>Pregnancy</topic><topic>Pregnancy Complications</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Tissue Inhibitor of Metalloproteinase-1 - metabolism</topic><topic>Tissue Inhibitor of Metalloproteinase-2 - metabolism</topic><topic>Tissue Inhibitor of Metalloproteinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tong, Wenni</creatorcontrib><creatorcontrib>Chen, Wanqiu</creatorcontrib><creatorcontrib>Ostrowski, Robert P.</creatorcontrib><creatorcontrib>Ma, Qingyi</creatorcontrib><creatorcontrib>Souvenir, Rhonda</creatorcontrib><creatorcontrib>Zhang, Lubo</creatorcontrib><creatorcontrib>Zhang, John H.</creatorcontrib><creatorcontrib>Tang, Jiping</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>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Developmental neurobiology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tong, Wenni</au><au>Chen, Wanqiu</au><au>Ostrowski, Robert P.</au><au>Ma, Qingyi</au><au>Souvenir, Rhonda</au><au>Zhang, Lubo</au><au>Zhang, John H.</au><au>Tang, Jiping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats</atitle><jtitle>Developmental neurobiology (Hoboken, N.J.)</jtitle><addtitle>Dev Neurobiol</addtitle><date>2010-02-15</date><risdate>2010</risdate><volume>70</volume><issue>3</issue><spage>182</spage><epage>194</epage><pages>182-194</pages><issn>1932-8451</issn><eissn>1932-846X</eissn><abstract>A recent study has shown that increased activity of matrix metalloproteinases‐2 and metalloproteinases‐9 (MMP‐2 and MMP‐9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP‐2 and MMP‐9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP‐1 and TIMP‐2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP‐2 and MMP‐9 and the protein abundance of TIMP‐1 and TIMP‐2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP‐2 at day 0, and increased MMP‐9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP‐2, MMP‐9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2010</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20017119</pmid><doi>10.1002/dneu.20770</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Newborn Brain - growth & development Brain - metabolism Cell Death chronic hypoxia development Female Hippocampus - growth & development Hippocampus - metabolism Hypoxia - complications maternal Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism matrix metalloproteinases Matrix Metalloproteinases - metabolism neonate Neurons - metabolism Neuropsychological Tests Pregnancy Pregnancy Complications Prenatal Exposure Delayed Effects Random Allocation Rats Rats, Sprague-Dawley Tissue Inhibitor of Metalloproteinase-1 - metabolism Tissue Inhibitor of Metalloproteinase-2 - metabolism Tissue Inhibitor of Metalloproteinases - metabolism |
| title | Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats |
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