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Progesterone in transient ischemic stroke: a dose–response study
Rationale Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking. Objectives We investigated the effects of progesterone at different doses on post-stroke brain in...
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| Published in: | Psychopharmacology 2014-09, Vol.231 (17), p.3313-3323 |
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| container_issue | 17 |
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| container_title | Psychopharmacology |
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| creator | Yousuf, Seema Atif, Fahim Sayeed, Iqbal Tang, Huiling Stein, Donald G. |
| description | Rationale
Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking.
Objectives
We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats.
Methods
Cerebral ischemia was induced in 13-month-old male Sprague–Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke.
Results
Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved (
p
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| doi_str_mv | 10.1007/s00213-014-3556-8 |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4134953</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A386595404</galeid><sourcerecordid>A386595404</sourcerecordid><originalsourceid>FETCH-LOGICAL-c603t-df71aa23fa781a8f501fc34d7abe84c1cad48275eefdb3cc7b2f8e8e119d5dfc3</originalsourceid><addsrcrecordid>eNp1kU1uFDEQhS0EIkPgAGxQS2yy6eDftocFUoj4kyKFBawtj12edOixB7sbKbvcITfMSajWhJCgYC8sub569qtHyEtGDxml-k2llDPRUiZboVTXmkdkwaTgLaeaPyYLSoVoBVNmjzyr9ZzikkY-JXtcasU7pRbk_deS11BHKDlB06dmLC7VHtLY9NWfwab3TR1L_gFvG9eEXOH68qpA3eZUAStTuHhOnkQ3VHhxc-6T7x8_fDv-3J6cfvpyfHTS-o6KsQ1RM-e4iE4b5kxUlEUvZNBuBUZ65l2QhmsFEMNKeK9XPBowwNgyqIDoPnm3091Oqw0Ej38sbrDb0m9cubDZ9fZ-JfVndp1_WcmEXCqBAgc3AiX_nNC03aBHGAaXIE_VMtVRRjulZ_T1P-h5nkpCe0gp0XGBY_1Lrd0Atk8x47t-FrVHwnRqqSSVSB0-QOEO83Rx7LHH-3sNbNfgS661QLz1yKidg7e74C0Gb-fgrcGeV3eHc9vxJ2kE-A6oWEprKHcc_Vf1NwwTueI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1553623315</pqid></control><display><type>article</type><title>Progesterone in transient ischemic stroke: a dose–response study</title><source>Springer Link</source><source>SPORTDiscus with Full Text</source><creator>Yousuf, Seema ; Atif, Fahim ; Sayeed, Iqbal ; Tang, Huiling ; Stein, Donald G.</creator><creatorcontrib>Yousuf, Seema ; Atif, Fahim ; Sayeed, Iqbal ; Tang, Huiling ; Stein, Donald G.</creatorcontrib><description>Rationale
Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking.
Objectives
We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats.
Methods
Cerebral ischemia was induced in 13-month-old male Sprague–Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke.
Results
Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved (
p
< 0.05) spatial memory performance. The P8 and P16 groups showed maximum improvement in long-term memory compared to vehicle. Significant (
p
< 0.05) gait impairments were observed in the vehicle group compared to shams. Animals receiving the P8 dose showed maximum gait improvement compared to vehicle. Post hoc analysis revealed that the P8 and P16 groups showed significant attenuation in infarct volume compared to vehicle. Animals receiving the P32 dose did not show any effect on infarct volume.
Conclusions
Although all doses were somewhat effective, progesterone given at 8 mg/kg led to the most consistent improvements across a panel of behavioral/functional tests and reduced the severity of ischemic infarct injury.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-014-3556-8</identifier><identifier>PMID: 24752655</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Behavior, Animal - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Dosage and administration ; Dose-Response Relationship, Drug ; Drug interactions ; Drug therapy ; Gait Disorders, Neurologic - drug therapy ; Hand Strength ; Identification and classification ; Infarction, Middle Cerebral Artery - drug therapy ; Infarction, Middle Cerebral Artery - pathology ; Infarction, Middle Cerebral Artery - psychology ; Ischemic Attack, Transient - drug therapy ; Ischemic Attack, Transient - pathology ; Ischemic Attack, Transient - psychology ; Male ; Maze Learning - drug effects ; Memory ; Memory - drug effects ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - therapeutic use ; Neurosciences ; Original Investigation ; Perceptual Disorders - drug therapy ; Perceptual Disorders - psychology ; Pharmacology/Toxicology ; Postural Balance - drug effects ; Progesterone ; Progesterone - administration & dosage ; Progesterone - therapeutic use ; Psychiatry ; Psychopharmacology ; Rats ; Rats, Sprague-Dawley ; Steroids ; Stroke ; Stroke (Disease)</subject><ispartof>Psychopharmacology, 2014-09, Vol.231 (17), p.3313-3323</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><rights>COPYRIGHT 2014 Springer</rights><rights>Springer-Verlag Berlin Heidelberg 2014 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-df71aa23fa781a8f501fc34d7abe84c1cad48275eefdb3cc7b2f8e8e119d5dfc3</citedby><cites>FETCH-LOGICAL-c603t-df71aa23fa781a8f501fc34d7abe84c1cad48275eefdb3cc7b2f8e8e119d5dfc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24752655$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yousuf, Seema</creatorcontrib><creatorcontrib>Atif, Fahim</creatorcontrib><creatorcontrib>Sayeed, Iqbal</creatorcontrib><creatorcontrib>Tang, Huiling</creatorcontrib><creatorcontrib>Stein, Donald G.</creatorcontrib><title>Progesterone in transient ischemic stroke: a dose–response study</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>Rationale
Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking.
Objectives
We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats.
Methods
Cerebral ischemia was induced in 13-month-old male Sprague–Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke.
Results
Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved (
p
< 0.05) spatial memory performance. The P8 and P16 groups showed maximum improvement in long-term memory compared to vehicle. Significant (
p
< 0.05) gait impairments were observed in the vehicle group compared to shams. Animals receiving the P8 dose showed maximum gait improvement compared to vehicle. Post hoc analysis revealed that the P8 and P16 groups showed significant attenuation in infarct volume compared to vehicle. Animals receiving the P32 dose did not show any effect on infarct volume.
Conclusions
Although all doses were somewhat effective, progesterone given at 8 mg/kg led to the most consistent improvements across a panel of behavioral/functional tests and reduced the severity of ischemic infarct injury.</description><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Dosage and administration</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug interactions</subject><subject>Drug therapy</subject><subject>Gait Disorders, Neurologic - drug therapy</subject><subject>Hand Strength</subject><subject>Identification and classification</subject><subject>Infarction, Middle Cerebral Artery - drug therapy</subject><subject>Infarction, Middle Cerebral Artery - pathology</subject><subject>Infarction, Middle Cerebral Artery - psychology</subject><subject>Ischemic Attack, Transient - drug therapy</subject><subject>Ischemic Attack, Transient - pathology</subject><subject>Ischemic Attack, Transient - psychology</subject><subject>Male</subject><subject>Maze Learning - drug effects</subject><subject>Memory</subject><subject>Memory - drug effects</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neurosciences</subject><subject>Original Investigation</subject><subject>Perceptual Disorders - drug therapy</subject><subject>Perceptual Disorders - psychology</subject><subject>Pharmacology/Toxicology</subject><subject>Postural Balance - drug effects</subject><subject>Progesterone</subject><subject>Progesterone - administration & dosage</subject><subject>Progesterone - therapeutic use</subject><subject>Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Steroids</subject><subject>Stroke</subject><subject>Stroke (Disease)</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNp1kU1uFDEQhS0EIkPgAGxQS2yy6eDftocFUoj4kyKFBawtj12edOixB7sbKbvcITfMSajWhJCgYC8sub569qtHyEtGDxml-k2llDPRUiZboVTXmkdkwaTgLaeaPyYLSoVoBVNmjzyr9ZzikkY-JXtcasU7pRbk_deS11BHKDlB06dmLC7VHtLY9NWfwab3TR1L_gFvG9eEXOH68qpA3eZUAStTuHhOnkQ3VHhxc-6T7x8_fDv-3J6cfvpyfHTS-o6KsQ1RM-e4iE4b5kxUlEUvZNBuBUZ65l2QhmsFEMNKeK9XPBowwNgyqIDoPnm3091Oqw0Ej38sbrDb0m9cubDZ9fZ-JfVndp1_WcmEXCqBAgc3AiX_nNC03aBHGAaXIE_VMtVRRjulZ_T1P-h5nkpCe0gp0XGBY_1Lrd0Atk8x47t-FrVHwnRqqSSVSB0-QOEO83Rx7LHH-3sNbNfgS661QLz1yKidg7e74C0Gb-fgrcGeV3eHc9vxJ2kE-A6oWEprKHcc_Vf1NwwTueI</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Yousuf, Seema</creator><creator>Atif, Fahim</creator><creator>Sayeed, Iqbal</creator><creator>Tang, Huiling</creator><creator>Stein, Donald G.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20140901</creationdate><title>Progesterone in transient ischemic stroke: a dose–response study</title><author>Yousuf, Seema ; Atif, Fahim ; Sayeed, Iqbal ; Tang, Huiling ; Stein, Donald G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c603t-df71aa23fa781a8f501fc34d7abe84c1cad48275eefdb3cc7b2f8e8e119d5dfc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Dosage and administration</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug interactions</topic><topic>Drug therapy</topic><topic>Gait Disorders, Neurologic - drug therapy</topic><topic>Hand Strength</topic><topic>Identification and classification</topic><topic>Infarction, Middle Cerebral Artery - drug therapy</topic><topic>Infarction, Middle Cerebral Artery - pathology</topic><topic>Infarction, Middle Cerebral Artery - psychology</topic><topic>Ischemic Attack, Transient - drug therapy</topic><topic>Ischemic Attack, Transient - pathology</topic><topic>Ischemic Attack, Transient - psychology</topic><topic>Male</topic><topic>Maze Learning - drug effects</topic><topic>Memory</topic><topic>Memory - drug effects</topic><topic>Neuroprotective Agents - administration & dosage</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Neurosciences</topic><topic>Original Investigation</topic><topic>Perceptual Disorders - drug therapy</topic><topic>Perceptual Disorders - psychology</topic><topic>Pharmacology/Toxicology</topic><topic>Postural Balance - drug effects</topic><topic>Progesterone</topic><topic>Progesterone - administration & dosage</topic><topic>Progesterone - therapeutic use</topic><topic>Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Steroids</topic><topic>Stroke</topic><topic>Stroke (Disease)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yousuf, Seema</creatorcontrib><creatorcontrib>Atif, Fahim</creatorcontrib><creatorcontrib>Sayeed, Iqbal</creatorcontrib><creatorcontrib>Tang, Huiling</creatorcontrib><creatorcontrib>Stein, Donald G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database (ProQuest)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yousuf, Seema</au><au>Atif, Fahim</au><au>Sayeed, Iqbal</au><au>Tang, Huiling</au><au>Stein, Donald G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Progesterone in transient ischemic stroke: a dose–response study</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>231</volume><issue>17</issue><spage>3313</spage><epage>3323</epage><pages>3313-3323</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><abstract>Rationale
Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking.
Objectives
We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats.
Methods
Cerebral ischemia was induced in 13-month-old male Sprague–Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke.
Results
Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved (
p
< 0.05) spatial memory performance. The P8 and P16 groups showed maximum improvement in long-term memory compared to vehicle. Significant (
p
< 0.05) gait impairments were observed in the vehicle group compared to shams. Animals receiving the P8 dose showed maximum gait improvement compared to vehicle. Post hoc analysis revealed that the P8 and P16 groups showed significant attenuation in infarct volume compared to vehicle. Animals receiving the P32 dose did not show any effect on infarct volume.
Conclusions
Although all doses were somewhat effective, progesterone given at 8 mg/kg led to the most consistent improvements across a panel of behavioral/functional tests and reduced the severity of ischemic infarct injury.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24752655</pmid><doi>10.1007/s00213-014-3556-8</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Psychopharmacology, 2014-09, Vol.231 (17), p.3313-3323 |
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| language | eng |
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| source | Springer Link; SPORTDiscus with Full Text |
| subjects | Animals Behavior, Animal - drug effects Biomedical and Life Sciences Biomedicine Dosage and administration Dose-Response Relationship, Drug Drug interactions Drug therapy Gait Disorders, Neurologic - drug therapy Hand Strength Identification and classification Infarction, Middle Cerebral Artery - drug therapy Infarction, Middle Cerebral Artery - pathology Infarction, Middle Cerebral Artery - psychology Ischemic Attack, Transient - drug therapy Ischemic Attack, Transient - pathology Ischemic Attack, Transient - psychology Male Maze Learning - drug effects Memory Memory - drug effects Neuroprotective Agents - administration & dosage Neuroprotective Agents - therapeutic use Neurosciences Original Investigation Perceptual Disorders - drug therapy Perceptual Disorders - psychology Pharmacology/Toxicology Postural Balance - drug effects Progesterone Progesterone - administration & dosage Progesterone - therapeutic use Psychiatry Psychopharmacology Rats Rats, Sprague-Dawley Steroids Stroke Stroke (Disease) |
| title | Progesterone in transient ischemic stroke: a dose–response study |
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