Aging exacerbates hypertension‐induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection
Summary Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal funct...
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| Veröffentlicht in: | Aging cell 2015-06, Vol.14 (3), p.400-408 |
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| creator | Toth, Peter Tarantini, Stefano Springo, Zsolt Tucsek, Zsuzsanna Gautam, Tripti Giles, Cory B. Wren, Jonathan D. Koller, Akos Sonntag, William E. Csiszar, Anna Ungvari, Zoltan |
| description | Summary
Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension‐induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L‐NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension‐induced cerebrovascular oxidative stress and redox‐sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension‐induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension‐induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high‐risk elderly patients. |
| doi_str_mv | 10.1111/acel.12315 |
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Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension‐induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L‐NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension‐induced cerebrovascular oxidative stress and redox‐sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension‐induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension‐induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high‐risk elderly patients.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.12315</identifier><identifier>PMID: 25677910</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Aging ; Animals ; arteriole ; Blood Pressure - drug effects ; Brain - drug effects ; Brain - metabolism ; cognitive impairment ; dementia ; Disease Models, Animal ; Hypertension - complications ; Hypertension - drug therapy ; Intracranial Hemorrhages - drug therapy ; Intracranial Hemorrhages - etiology ; Intracranial Hemorrhages - prevention & control ; Male ; Mice, Inbred C57BL ; microbleed ; NADPH oxidase ; Original ; Oxidation-Reduction - drug effects ; oxidative stress ; Oxidative Stress - drug effects ; Stilbenes - pharmacology</subject><ispartof>Aging cell, 2015-06, Vol.14 (3), p.400-408</ispartof><rights>2015 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>Copyright © 2015 The Anatomical Society and John Wiley & Sons Ltd</rights><rights>2015 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5925-4b3c7f51039505f3bb30a00f0b18a85ee6e7709ceb7cbf830d7e50a896edae433</citedby><cites>FETCH-LOGICAL-c5925-4b3c7f51039505f3bb30a00f0b18a85ee6e7709ceb7cbf830d7e50a896edae433</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/PMC4406669/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406669/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11543,27903,27904,45553,45554,46030,46454,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25677910$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toth, Peter</creatorcontrib><creatorcontrib>Tarantini, Stefano</creatorcontrib><creatorcontrib>Springo, Zsolt</creatorcontrib><creatorcontrib>Tucsek, Zsuzsanna</creatorcontrib><creatorcontrib>Gautam, Tripti</creatorcontrib><creatorcontrib>Giles, Cory B.</creatorcontrib><creatorcontrib>Wren, Jonathan D.</creatorcontrib><creatorcontrib>Koller, Akos</creatorcontrib><creatorcontrib>Sonntag, William E.</creatorcontrib><creatorcontrib>Csiszar, Anna</creatorcontrib><creatorcontrib>Ungvari, Zoltan</creatorcontrib><title>Aging exacerbates hypertension‐induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>Summary
Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension‐induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L‐NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension‐induced cerebrovascular oxidative stress and redox‐sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension‐induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension‐induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high‐risk elderly patients.</description><subject>Aging</subject><subject>Animals</subject><subject>arteriole</subject><subject>Blood Pressure - drug effects</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>cognitive impairment</subject><subject>dementia</subject><subject>Disease Models, Animal</subject><subject>Hypertension - complications</subject><subject>Hypertension - drug therapy</subject><subject>Intracranial Hemorrhages - drug therapy</subject><subject>Intracranial Hemorrhages - etiology</subject><subject>Intracranial Hemorrhages - prevention & control</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>microbleed</subject><subject>NADPH oxidase</subject><subject>Original</subject><subject>Oxidation-Reduction - drug effects</subject><subject>oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Stilbenes - pharmacology</subject><issn>1474-9718</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkcuKFDEUQIMozji68QOkwI0IPSaVSlJxMdA04wMa3Og6JKlb3RmqkjZJtTZu_AS_0S8xZY-NuhCzyeOeHO4DoccEX5KyXmgLwyWpKWF30DlpRLOQouZ3T2fSnqEHKd1gTITE9D46qxkXQhJ8jr4sN85vKvhcJNHoDKnaHnYQM_jkgv_-9Zvz3WShq0ocTNRDNTobwxbGEONWb8oH5-c3eFnFMEAV-ipC2kPUudyrHEHnEXyesb1OYRdDBpuL_CG61-shwaPb_QJ9eHX9fvVmsX73-u1quV5YJmu2aAy1omcEU8kw66kxFGuMe2xIq1sGwEEILC0YYU3fUtwJYFi3kkOnoaH0Al0dvbvJjNDZkkypQ-2iG3U8qKCd-jPi3VZtwl41DeacyyJ4diuI4eMEKavRpdL0QXsIU1KEt7iwLWf_gYqmJjVns_XpX-hNmKIvnZgpSgiXDSnU8yNVmp5ShP6UN8FqHr-ax69-jr_AT36v9IT-mncByBH45AY4_EOllqvr9VH6A5tOvs4</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Toth, Peter</creator><creator>Tarantini, Stefano</creator><creator>Springo, Zsolt</creator><creator>Tucsek, Zsuzsanna</creator><creator>Gautam, Tripti</creator><creator>Giles, Cory B.</creator><creator>Wren, Jonathan D.</creator><creator>Koller, Akos</creator><creator>Sonntag, William E.</creator><creator>Csiszar, Anna</creator><creator>Ungvari, Zoltan</creator><general>John Wiley & Sons, Inc</general><general>BlackWell Publishing Ltd</general><scope>24P</scope><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>7QP</scope><scope>7TK</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201506</creationdate><title>Aging exacerbates hypertension‐induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection</title><author>Toth, Peter ; Tarantini, Stefano ; Springo, Zsolt ; Tucsek, Zsuzsanna ; Gautam, Tripti ; Giles, Cory B. ; Wren, Jonathan D. ; Koller, Akos ; Sonntag, William E. ; Csiszar, Anna ; Ungvari, Zoltan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5925-4b3c7f51039505f3bb30a00f0b18a85ee6e7709ceb7cbf830d7e50a896edae433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aging</topic><topic>Animals</topic><topic>arteriole</topic><topic>Blood Pressure - drug effects</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>cognitive impairment</topic><topic>dementia</topic><topic>Disease Models, Animal</topic><topic>Hypertension - complications</topic><topic>Hypertension - drug therapy</topic><topic>Intracranial Hemorrhages - drug therapy</topic><topic>Intracranial Hemorrhages - etiology</topic><topic>Intracranial Hemorrhages - prevention & control</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>microbleed</topic><topic>NADPH oxidase</topic><topic>Original</topic><topic>Oxidation-Reduction - drug effects</topic><topic>oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Stilbenes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toth, Peter</creatorcontrib><creatorcontrib>Tarantini, Stefano</creatorcontrib><creatorcontrib>Springo, Zsolt</creatorcontrib><creatorcontrib>Tucsek, Zsuzsanna</creatorcontrib><creatorcontrib>Gautam, Tripti</creatorcontrib><creatorcontrib>Giles, Cory B.</creatorcontrib><creatorcontrib>Wren, Jonathan D.</creatorcontrib><creatorcontrib>Koller, Akos</creatorcontrib><creatorcontrib>Sonntag, William E.</creatorcontrib><creatorcontrib>Csiszar, Anna</creatorcontrib><creatorcontrib>Ungvari, Zoltan</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toth, Peter</au><au>Tarantini, Stefano</au><au>Springo, Zsolt</au><au>Tucsek, Zsuzsanna</au><au>Gautam, Tripti</au><au>Giles, Cory B.</au><au>Wren, Jonathan D.</au><au>Koller, Akos</au><au>Sonntag, William E.</au><au>Csiszar, Anna</au><au>Ungvari, Zoltan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aging exacerbates hypertension‐induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2015-06</date><risdate>2015</risdate><volume>14</volume><issue>3</issue><spage>400</spage><epage>408</epage><pages>400-408</pages><issn>1474-9718</issn><eissn>1474-9726</eissn><abstract>Summary
Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension‐induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L‐NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension‐induced cerebrovascular oxidative stress and redox‐sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension‐induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension‐induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high‐risk elderly patients.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>25677910</pmid><doi>10.1111/acel.12315</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aging Animals arteriole Blood Pressure - drug effects Brain - drug effects Brain - metabolism cognitive impairment dementia Disease Models, Animal Hypertension - complications Hypertension - drug therapy Intracranial Hemorrhages - drug therapy Intracranial Hemorrhages - etiology Intracranial Hemorrhages - prevention & control Male Mice, Inbred C57BL microbleed NADPH oxidase Original Oxidation-Reduction - drug effects oxidative stress Oxidative Stress - drug effects Stilbenes - pharmacology |
| title | Aging exacerbates hypertension‐induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection |
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