The impact of single and combined PPAR-α and PPAR-γ activation on the neurological outcomes following cerebral ischemia reperfusion
The neuronal damage and accompanied functional deficits induced by cerebral ischemia are among the most common causes of disabilities in adults. Activation of subtypes of peroxisome proliferator-activated receptors (PPARs); PPAR-α and PPAR-γ have shown neuroprotective effects in different neurodegen...
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| Veröffentlicht in: | Life sciences (1973) 2020-07, Vol.252, p.117679-10, Article 117679 |
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| creator | Shehata, Alaa H.F. Ahmed, Al-Shaimaa F. Abdelrehim, Amany B. Heeba, Gehan H. |
| description | The neuronal damage and accompanied functional deficits induced by cerebral ischemia are among the most common causes of disabilities in adults. Activation of subtypes of peroxisome proliferator-activated receptors (PPARs); PPAR-α and PPAR-γ have shown neuroprotective effects in different neurodegenerative diseases including stroke. Thus, this study aimed to compare the effects of two different agonists: PPAR-α (fenofibrate) and PPAR-γ (pioglitazone) as well as the effect of their combination in ameliorating post-ischemia behavioral deficits.
Male Wistar rats were either pretreated with vehicle, fenofibrate (100 mg/kg/day p.o), pioglitazone (10 mg/kg/day p.o) or their combination for 14 days prior to bilateral common carotid artery occlusion followed by reperfusion for 24 hoursh. The sensory motor functions of rats were assessed, then rats were sacrificed to determine infarct volume and histopathological changes as well as oxidative stress, inflammatory and apoptotic markers in the brain tissue.
Pre-treatment with fenofibrate and pioglitazone in addition to their combination improved neurobehavioral dysfunction, reduced cerebral infarct volume, attenuated inflammatory and apoptotic markers and ameliorated histopathological changes in I/R injured rats. The effect of pioglitazone in cerebral cortex was higher than its corresponding effect in fenofibrate while the combined administration of both drugs had additive neuroprotective effect and normalized inflammatory and apoptotic mediators in ischemic rats.
The study compared the neuroprotective effects of PPAR-α and PPAR-γ agonists, and tested the impact of their combination. We concluded that no additional benefits on the functional outcomes might be gained upon their combination. |
| doi_str_mv | 10.1016/j.lfs.2020.117679 |
| format | Article |
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Male Wistar rats were either pretreated with vehicle, fenofibrate (100 mg/kg/day p.o), pioglitazone (10 mg/kg/day p.o) or their combination for 14 days prior to bilateral common carotid artery occlusion followed by reperfusion for 24 hoursh. The sensory motor functions of rats were assessed, then rats were sacrificed to determine infarct volume and histopathological changes as well as oxidative stress, inflammatory and apoptotic markers in the brain tissue.
Pre-treatment with fenofibrate and pioglitazone in addition to their combination improved neurobehavioral dysfunction, reduced cerebral infarct volume, attenuated inflammatory and apoptotic markers and ameliorated histopathological changes in I/R injured rats. The effect of pioglitazone in cerebral cortex was higher than its corresponding effect in fenofibrate while the combined administration of both drugs had additive neuroprotective effect and normalized inflammatory and apoptotic mediators in ischemic rats.
The study compared the neuroprotective effects of PPAR-α and PPAR-γ agonists, and tested the impact of their combination. We concluded that no additional benefits on the functional outcomes might be gained upon their combination.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2020.117679</identifier><identifier>PMID: 32325134</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Agonists ; Apoptosis ; Behavioral deficits ; Carotid artery ; Cerebral blood flow ; Cerebral cortex ; Cerebral infarction ; Cerebral ischemia reperfusion ; Cortex (somatosensory) ; Disabilities ; Fenofibrate ; Inflammation ; Ischemia ; Ladder test ; Markers ; Neurodegenerative diseases ; Neuroprotection ; Occlusion ; Open field test ; Oxidative stress ; Peroxisome proliferator-activated receptors ; Pioglitazone ; Pretreatment ; Reperfusion ; Rodents ; Tape removal test</subject><ispartof>Life sciences (1973), 2020-07, Vol.252, p.117679-10, Article 117679</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Jul 1, 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-8c649bf77ac5eb2fc93afef66705da29cbb7690db867b820024375048928aabb3</citedby><cites>FETCH-LOGICAL-c381t-8c649bf77ac5eb2fc93afef66705da29cbb7690db867b820024375048928aabb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320520304276$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32325134$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shehata, Alaa H.F.</creatorcontrib><creatorcontrib>Ahmed, Al-Shaimaa F.</creatorcontrib><creatorcontrib>Abdelrehim, Amany B.</creatorcontrib><creatorcontrib>Heeba, Gehan H.</creatorcontrib><title>The impact of single and combined PPAR-α and PPAR-γ activation on the neurological outcomes following cerebral ischemia reperfusion</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>The neuronal damage and accompanied functional deficits induced by cerebral ischemia are among the most common causes of disabilities in adults. Activation of subtypes of peroxisome proliferator-activated receptors (PPARs); PPAR-α and PPAR-γ have shown neuroprotective effects in different neurodegenerative diseases including stroke. Thus, this study aimed to compare the effects of two different agonists: PPAR-α (fenofibrate) and PPAR-γ (pioglitazone) as well as the effect of their combination in ameliorating post-ischemia behavioral deficits.
Male Wistar rats were either pretreated with vehicle, fenofibrate (100 mg/kg/day p.o), pioglitazone (10 mg/kg/day p.o) or their combination for 14 days prior to bilateral common carotid artery occlusion followed by reperfusion for 24 hoursh. The sensory motor functions of rats were assessed, then rats were sacrificed to determine infarct volume and histopathological changes as well as oxidative stress, inflammatory and apoptotic markers in the brain tissue.
Pre-treatment with fenofibrate and pioglitazone in addition to their combination improved neurobehavioral dysfunction, reduced cerebral infarct volume, attenuated inflammatory and apoptotic markers and ameliorated histopathological changes in I/R injured rats. The effect of pioglitazone in cerebral cortex was higher than its corresponding effect in fenofibrate while the combined administration of both drugs had additive neuroprotective effect and normalized inflammatory and apoptotic mediators in ischemic rats.
The study compared the neuroprotective effects of PPAR-α and PPAR-γ agonists, and tested the impact of their combination. We concluded that no additional benefits on the functional outcomes might be gained upon their combination.</description><subject>Agonists</subject><subject>Apoptosis</subject><subject>Behavioral deficits</subject><subject>Carotid artery</subject><subject>Cerebral blood flow</subject><subject>Cerebral cortex</subject><subject>Cerebral infarction</subject><subject>Cerebral ischemia reperfusion</subject><subject>Cortex (somatosensory)</subject><subject>Disabilities</subject><subject>Fenofibrate</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>Ladder test</subject><subject>Markers</subject><subject>Neurodegenerative diseases</subject><subject>Neuroprotection</subject><subject>Occlusion</subject><subject>Open field test</subject><subject>Oxidative stress</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Pioglitazone</subject><subject>Pretreatment</subject><subject>Reperfusion</subject><subject>Rodents</subject><subject>Tape removal test</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kc1qFTEYhoMo9li9ADcScONmTvMzkx9claJVKLRIXYck86XNYWZyTGYqXoAXJN5Hr8kcp7pwIQTy93wPX_Ii9JKSLSVUnOy2QyhbRljdUymkfoQ2VEndEMHpY7QhhLUNZ6Q7Qs9K2RFCuk7yp-iIM846ytsN-n59CziOe-tnnAIucboZANupxz6NLk7Q46ur00_N_Y_fh-v6J654vLNzTBOuY66OCZachnQTvR1wWuZaDgWHNAzpa5ViDxlcrnex-FsYo8UZ9pDDUqrkOXoS7FDgxcN8jD6_f3d99qG5uDz_eHZ60Xiu6NwoL1rtgpTWd-BY8JrbAEEISbreMu2dk0KT3ikhnWKH53PZkVZppqx1jh-jN6t3n9OXBcpsxtoODIOdIC3FMK5bTVTb8Yq-_gfdpSVPtTvDWqG1Eq1ilaIr5XMqJUMw-xxHm78ZSswhI7MzNSNzyMisGdWaVw_mxY3Q_634E0oF3q4A1K-4i5BN8REmD33M4GfTp_gf_S8tyqOy</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Shehata, Alaa H.F.</creator><creator>Ahmed, Al-Shaimaa F.</creator><creator>Abdelrehim, Amany B.</creator><creator>Heeba, Gehan H.</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20200701</creationdate><title>The impact of single and combined PPAR-α and PPAR-γ activation on the neurological outcomes following cerebral ischemia reperfusion</title><author>Shehata, Alaa H.F. ; Ahmed, Al-Shaimaa F. ; Abdelrehim, Amany B. ; Heeba, Gehan H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-8c649bf77ac5eb2fc93afef66705da29cbb7690db867b820024375048928aabb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Agonists</topic><topic>Apoptosis</topic><topic>Behavioral deficits</topic><topic>Carotid artery</topic><topic>Cerebral blood flow</topic><topic>Cerebral cortex</topic><topic>Cerebral infarction</topic><topic>Cerebral ischemia reperfusion</topic><topic>Cortex (somatosensory)</topic><topic>Disabilities</topic><topic>Fenofibrate</topic><topic>Inflammation</topic><topic>Ischemia</topic><topic>Ladder test</topic><topic>Markers</topic><topic>Neurodegenerative diseases</topic><topic>Neuroprotection</topic><topic>Occlusion</topic><topic>Open field test</topic><topic>Oxidative stress</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Pioglitazone</topic><topic>Pretreatment</topic><topic>Reperfusion</topic><topic>Rodents</topic><topic>Tape removal test</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shehata, Alaa H.F.</creatorcontrib><creatorcontrib>Ahmed, Al-Shaimaa F.</creatorcontrib><creatorcontrib>Abdelrehim, Amany B.</creatorcontrib><creatorcontrib>Heeba, Gehan H.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shehata, Alaa H.F.</au><au>Ahmed, Al-Shaimaa F.</au><au>Abdelrehim, Amany B.</au><au>Heeba, Gehan H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The impact of single and combined PPAR-α and PPAR-γ activation on the neurological outcomes following cerebral ischemia reperfusion</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>252</volume><spage>117679</spage><epage>10</epage><pages>117679-10</pages><artnum>117679</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>The neuronal damage and accompanied functional deficits induced by cerebral ischemia are among the most common causes of disabilities in adults. Activation of subtypes of peroxisome proliferator-activated receptors (PPARs); PPAR-α and PPAR-γ have shown neuroprotective effects in different neurodegenerative diseases including stroke. Thus, this study aimed to compare the effects of two different agonists: PPAR-α (fenofibrate) and PPAR-γ (pioglitazone) as well as the effect of their combination in ameliorating post-ischemia behavioral deficits.
Male Wistar rats were either pretreated with vehicle, fenofibrate (100 mg/kg/day p.o), pioglitazone (10 mg/kg/day p.o) or their combination for 14 days prior to bilateral common carotid artery occlusion followed by reperfusion for 24 hoursh. The sensory motor functions of rats were assessed, then rats were sacrificed to determine infarct volume and histopathological changes as well as oxidative stress, inflammatory and apoptotic markers in the brain tissue.
Pre-treatment with fenofibrate and pioglitazone in addition to their combination improved neurobehavioral dysfunction, reduced cerebral infarct volume, attenuated inflammatory and apoptotic markers and ameliorated histopathological changes in I/R injured rats. The effect of pioglitazone in cerebral cortex was higher than its corresponding effect in fenofibrate while the combined administration of both drugs had additive neuroprotective effect and normalized inflammatory and apoptotic mediators in ischemic rats.
The study compared the neuroprotective effects of PPAR-α and PPAR-γ agonists, and tested the impact of their combination. We concluded that no additional benefits on the functional outcomes might be gained upon their combination.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>32325134</pmid><doi>10.1016/j.lfs.2020.117679</doi><tpages>10</tpages></addata></record> |
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| subjects | Agonists Apoptosis Behavioral deficits Carotid artery Cerebral blood flow Cerebral cortex Cerebral infarction Cerebral ischemia reperfusion Cortex (somatosensory) Disabilities Fenofibrate Inflammation Ischemia Ladder test Markers Neurodegenerative diseases Neuroprotection Occlusion Open field test Oxidative stress Peroxisome proliferator-activated receptors Pioglitazone Pretreatment Reperfusion Rodents Tape removal test |
| title | The impact of single and combined PPAR-α and PPAR-γ activation on the neurological outcomes following cerebral ischemia reperfusion |
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