Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia
Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behav...
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| Veröffentlicht in: | Stroke (1970) 1995-03, Vol.26 (3), p.466-472 |
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| creator | Wiard, R P Dickerson, M C Beek, O Norton, R Cooper, B R |
| description | Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behavioral and histological measures of global ischemia in gerbils.
The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated.
Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia.
Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia. |
| doi_str_mv | 10.1161/01.STR.26.3.466 |
| format | Article |
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The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated.
Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia.
Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/01.STR.26.3.466</identifier><identifier>PMID: 7886726</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Animals ; Anticonvulsants - administration & dosage ; Anticonvulsants - blood ; Anticonvulsants - therapeutic use ; Arterial Occlusive Diseases - physiopathology ; Behavior, Animal - drug effects ; Behavior, Animal - physiology ; Brain Chemistry ; Brain Ischemia - pathology ; Brain Ischemia - physiopathology ; Brain Ischemia - prevention & control ; Carotid Artery Diseases - physiopathology ; Cell Death - drug effects ; Cognition - drug effects ; Cognition - physiology ; Disease Models, Animal ; Gerbillinae ; Glutamic Acid - metabolism ; Hippocampus - drug effects ; Hippocampus - pathology ; Lamotrigine ; Male ; Memory - drug effects ; Memory - physiology ; Nerve Degeneration - drug effects ; Neurons - drug effects ; Neurons - pathology ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - blood ; Neuroprotective Agents - therapeutic use ; Pyramidal Cells - drug effects ; Pyramidal Cells - pathology ; Reperfusion Injury - pathology ; Reperfusion Injury - prevention & control ; Triazines - administration & dosage ; Triazines - blood ; Triazines - therapeutic use</subject><ispartof>Stroke (1970), 1995-03, Vol.26 (3), p.466-472</ispartof><rights>Copyright American Heart Association, Inc. Mar 1995</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-23eedb41a9ff787c72f3c71007eed2a8bb1525ec73990f7d553b60bdfa111ab63</citedby><cites>FETCH-LOGICAL-c354t-23eedb41a9ff787c72f3c71007eed2a8bb1525ec73990f7d553b60bdfa111ab63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7886726$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wiard, R P</creatorcontrib><creatorcontrib>Dickerson, M C</creatorcontrib><creatorcontrib>Beek, O</creatorcontrib><creatorcontrib>Norton, R</creatorcontrib><creatorcontrib>Cooper, B R</creatorcontrib><title>Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behavioral and histological measures of global ischemia in gerbils.
The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated.
Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia.
Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia.</description><subject>Animals</subject><subject>Anticonvulsants - administration & dosage</subject><subject>Anticonvulsants - blood</subject><subject>Anticonvulsants - therapeutic use</subject><subject>Arterial Occlusive Diseases - physiopathology</subject><subject>Behavior, Animal - drug effects</subject><subject>Behavior, Animal - physiology</subject><subject>Brain Chemistry</subject><subject>Brain Ischemia - pathology</subject><subject>Brain Ischemia - physiopathology</subject><subject>Brain Ischemia - prevention & control</subject><subject>Carotid Artery Diseases - physiopathology</subject><subject>Cell Death - drug effects</subject><subject>Cognition - drug effects</subject><subject>Cognition - physiology</subject><subject>Disease Models, Animal</subject><subject>Gerbillinae</subject><subject>Glutamic Acid - metabolism</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - pathology</subject><subject>Lamotrigine</subject><subject>Male</subject><subject>Memory - drug effects</subject><subject>Memory - physiology</subject><subject>Nerve Degeneration - drug effects</subject><subject>Neurons - drug effects</subject><subject>Neurons - pathology</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>Neuroprotective Agents - blood</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Pyramidal Cells - drug effects</subject><subject>Pyramidal Cells - pathology</subject><subject>Reperfusion Injury - pathology</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Triazines - administration & dosage</subject><subject>Triazines - blood</subject><subject>Triazines - therapeutic use</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1r3DAQxUVJSTfbnnsqiBxys6MPW7KOJeQLlhaa9CwkebxRkC1Xshfy31dllx5ymmH4zWPePIS-UlJTKug1ofXT86-aiZrXjRAf0Ia2rKkawboztCGEq4o1Sn1CFzm_EkIY79pzdC67TkgmNij-gDXFOcUF3OIPgEs7Q1o8ZBwHvLwAnuIBAjZTmc0-wLx4h4MZ45L83k-A_YQN3kOyPuAx9oUti_sQrQnYQQKbSuOze4HRm8_o42BChi-nukW_726fbx6q3c_7x5vvu8rxtlkqxgF621CjhkF20kk2cCcpIbLMmemsLTZbcJIrRQbZty23gth-MJRSYwXfoqujbvHzZ4W86LGcACGYCeKatZRUcqlUAS_fga9xTVO5TVMlJaNt1xXo-gi5FHNOMOg5-dGkN02J_peDJlSXHDQTmuuSQ9n4dpJd7Qj9f_70eP4Xp3SFeg</recordid><startdate>19950301</startdate><enddate>19950301</enddate><creator>Wiard, R P</creator><creator>Dickerson, M C</creator><creator>Beek, O</creator><creator>Norton, R</creator><creator>Cooper, B R</creator><general>American Heart Association, 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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>19950301</creationdate><title>Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia</title><author>Wiard, R P ; Dickerson, M C ; Beek, O ; Norton, R ; Cooper, B R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-23eedb41a9ff787c72f3c71007eed2a8bb1525ec73990f7d553b60bdfa111ab63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Anticonvulsants - administration & dosage</topic><topic>Anticonvulsants - blood</topic><topic>Anticonvulsants - therapeutic use</topic><topic>Arterial Occlusive Diseases - physiopathology</topic><topic>Behavior, Animal - drug effects</topic><topic>Behavior, Animal - physiology</topic><topic>Brain Chemistry</topic><topic>Brain Ischemia - pathology</topic><topic>Brain Ischemia - physiopathology</topic><topic>Brain Ischemia - prevention & control</topic><topic>Carotid Artery Diseases - physiopathology</topic><topic>Cell Death - drug effects</topic><topic>Cognition - drug effects</topic><topic>Cognition - physiology</topic><topic>Disease Models, Animal</topic><topic>Gerbillinae</topic><topic>Glutamic Acid - metabolism</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - pathology</topic><topic>Lamotrigine</topic><topic>Male</topic><topic>Memory - drug effects</topic><topic>Memory - physiology</topic><topic>Nerve Degeneration - drug effects</topic><topic>Neurons - drug effects</topic><topic>Neurons - pathology</topic><topic>Neuroprotective Agents - administration & dosage</topic><topic>Neuroprotective Agents - blood</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Pyramidal Cells - drug effects</topic><topic>Pyramidal Cells - pathology</topic><topic>Reperfusion Injury - pathology</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Triazines - administration & dosage</topic><topic>Triazines - blood</topic><topic>Triazines - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wiard, R P</creatorcontrib><creatorcontrib>Dickerson, M C</creatorcontrib><creatorcontrib>Beek, O</creatorcontrib><creatorcontrib>Norton, R</creatorcontrib><creatorcontrib>Cooper, B R</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 Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wiard, R P</au><au>Dickerson, M C</au><au>Beek, O</au><au>Norton, R</au><au>Cooper, B R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>1995-03-01</date><risdate>1995</risdate><volume>26</volume><issue>3</issue><spage>466</spage><epage>472</epage><pages>466-472</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>Elevated glutamate levels are thought to be a primary cause of neuronal death after global cerebral ischemia. The purpose of this study was to investigate the potential neuroprotective effects of lamotrigine, a novel antiepileptic drug that inhibits the release of glutamate in vitro, with both behavioral and histological measures of global ischemia in gerbils.
The common carotid arteries of gerbils were occluded for either 5, 10, or 15 minutes. Twenty-one days after reperfusion, gerbils were tested for impairments in a spatial memory task (Morris water maze). After water maze testing the animals were killed, and damage to hippocampal pyramidal cells was assessed. The effect of lamotrigine on the behavioral and histological outcome of either 5 or 15 minutes of global ischemia was evaluated.
Bilateral occlusion of the common carotid arteries for 5 minutes resulted in severe degeneration of hippocampal CA1 and CA2 pyramidal cells. Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion. Gerbils subjected to 5 minutes of ischemic insult were not impaired in their ability to solve a spatial memory task 21 days after cerebral ischemia. However, gerbils subjected to 10 and 15 minutes of carotid artery occlusion showed significant impairment in their ability to solve a water maze task. Lamotrigine significantly protected against the cognitive deficits associated with 15 minutes of cerebral ischemia. Histologically, increased durations of cerebral ischemia resulted in a progressive loss of CA1, CA2, and CA3 pyramidal cells. Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus. Lamotrigine also reduced the mortality associated with 15 minutes of ischemia.
Lamotrigine had neuroprotective effects in a gerbil model of global cerebral ischemia. Lamotrigine protected gerbils against behavioral deficits resulting from 15 minutes of carotid occlusion and also prevented histological damage resulting from 5 and 15 minutes of global cerebral ischemia.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>7886726</pmid><doi>10.1161/01.STR.26.3.466</doi><tpages>7</tpages></addata></record> |
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| ispartof | Stroke (1970), 1995-03, Vol.26 (3), p.466-472 |
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| source | Journals@Ovid Ovid Autoload; MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library; American Heart Association |
| subjects | Animals Anticonvulsants - administration & dosage Anticonvulsants - blood Anticonvulsants - therapeutic use Arterial Occlusive Diseases - physiopathology Behavior, Animal - drug effects Behavior, Animal - physiology Brain Chemistry Brain Ischemia - pathology Brain Ischemia - physiopathology Brain Ischemia - prevention & control Carotid Artery Diseases - physiopathology Cell Death - drug effects Cognition - drug effects Cognition - physiology Disease Models, Animal Gerbillinae Glutamic Acid - metabolism Hippocampus - drug effects Hippocampus - pathology Lamotrigine Male Memory - drug effects Memory - physiology Nerve Degeneration - drug effects Neurons - drug effects Neurons - pathology Neuroprotective Agents - administration & dosage Neuroprotective Agents - blood Neuroprotective Agents - therapeutic use Pyramidal Cells - drug effects Pyramidal Cells - pathology Reperfusion Injury - pathology Reperfusion Injury - prevention & control Triazines - administration & dosage Triazines - blood Triazines - therapeutic use |
| title | Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia |
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