Selective γ-aminobutyric acid type a receptor antagonism reverses isoflurane ischemic neuroprotection
Isoflurane provides protection against severe forebrain ischemia in the rat. The authors hypothesized that this is attributable to interaction with the gamma-aminobutyric acid type A (GABAA) receptor resulting in altered time to onset of ischemic hippocampal depolarization. Organotypic hippocampal s...
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| Veröffentlicht in: | Anesthesiology (Philadelphia) 2006-07, Vol.105 (1), p.81-90 |
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| creator | ELSERSY, Hazem MIXCO, Javier HUAXIN SHENG PEARLSTEIN, Robert D WARNER, David S |
| description | Isoflurane provides protection against severe forebrain ischemia in the rat. The authors hypothesized that this is attributable to interaction with the gamma-aminobutyric acid type A (GABAA) receptor resulting in altered time to onset of ischemic hippocampal depolarization.
Organotypic hippocampal slices were subjected to oxygen-glucose deprivation in the presence of isoflurane and combinations of GABAA (bicuculline) and GABAB (phaclofen) receptor antagonists. Cell death was measured. Rats were subjected to severe forebrain ischemia while anesthetized with fentanyl-nitrous oxide or 1.4% isoflurane. In the isoflurane group, rats also received intravenous bicuculline (0, 1, or 2 mg/kg). Neurologic and histologic outcomes and time to depolarization were assessed.
In slices, 2% isoflurane caused near-complete protection against oxygen-glucose deprivation. This was unaffected by coadministration of phaclofen but largely reversed by bicuculline. The GABAA agonist muscimol was also protective, having an effect equivalent to 1% isoflurane. In rats, isoflurane (0 mg bicuculline) improved neurologic and histologic outcome versus fentanyl-nitrous oxide (CA1 percentage of alive neurons: fentanyl-nitrous oxide, 15 +/- 7; isoflurane, 61 +/- 24). The isoflurane effect was reversed in a dose-dependent manner by bicuculline (CA1 percentage alive: 1 mg/kg, 44 +/- 22; 2 mg/kg, 21 +/- 15). Time to depolarization was delayed with isoflurane versus fentanyl-nitrous oxide (137 vs. 80 s) but was not affected by bicuculline (149 s). In contrast, postischemic time to repolarization was more rapid with fentanyl-nitrous oxide or isoflurane plus bicuculline versus isoflurane alone.
These studies are consistent with the hypothesis that the GABAA receptor serves as a major site of action for isoflurane neuroprotection both in vitro and in vivo. However, the mechanism by which this interaction confers in vivo protection cannot be attributed to effects on the duration of ischemic depolarization. |
| doi_str_mv | 10.1097/00000542-200607000-00016 |
| format | Article |
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Organotypic hippocampal slices were subjected to oxygen-glucose deprivation in the presence of isoflurane and combinations of GABAA (bicuculline) and GABAB (phaclofen) receptor antagonists. Cell death was measured. Rats were subjected to severe forebrain ischemia while anesthetized with fentanyl-nitrous oxide or 1.4% isoflurane. In the isoflurane group, rats also received intravenous bicuculline (0, 1, or 2 mg/kg). Neurologic and histologic outcomes and time to depolarization were assessed.
In slices, 2% isoflurane caused near-complete protection against oxygen-glucose deprivation. This was unaffected by coadministration of phaclofen but largely reversed by bicuculline. The GABAA agonist muscimol was also protective, having an effect equivalent to 1% isoflurane. In rats, isoflurane (0 mg bicuculline) improved neurologic and histologic outcome versus fentanyl-nitrous oxide (CA1 percentage of alive neurons: fentanyl-nitrous oxide, 15 +/- 7; isoflurane, 61 +/- 24). The isoflurane effect was reversed in a dose-dependent manner by bicuculline (CA1 percentage alive: 1 mg/kg, 44 +/- 22; 2 mg/kg, 21 +/- 15). Time to depolarization was delayed with isoflurane versus fentanyl-nitrous oxide (137 vs. 80 s) but was not affected by bicuculline (149 s). In contrast, postischemic time to repolarization was more rapid with fentanyl-nitrous oxide or isoflurane plus bicuculline versus isoflurane alone.
These studies are consistent with the hypothesis that the GABAA receptor serves as a major site of action for isoflurane neuroprotection both in vitro and in vivo. However, the mechanism by which this interaction confers in vivo protection cannot be attributed to effects on the duration of ischemic depolarization.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/00000542-200607000-00016</identifier><identifier>PMID: 16809998</identifier><identifier>CODEN: ANESAV</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Anesthesia ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Biological and medical sciences ; Brain Ischemia - physiopathology ; Brain Ischemia - prevention & control ; GABA Antagonists - pharmacology ; GABA-A Receptor Antagonists ; In Vitro Techniques ; Isoflurane - antagonists & inhibitors ; Isoflurane - therapeutic use ; Medical sciences ; Neuroprotective Agents - antagonists & inhibitors ; Neuroprotective Agents - therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A - physiology</subject><ispartof>Anesthesiology (Philadelphia), 2006-07, Vol.105 (1), p.81-90</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3086-ca19d05f0426b83eb1d2191165d949d5e0cf353c0efd28b6ab7fc520af6284733</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17919788$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16809998$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ELSERSY, Hazem</creatorcontrib><creatorcontrib>MIXCO, Javier</creatorcontrib><creatorcontrib>HUAXIN SHENG</creatorcontrib><creatorcontrib>PEARLSTEIN, Robert D</creatorcontrib><creatorcontrib>WARNER, David S</creatorcontrib><title>Selective γ-aminobutyric acid type a receptor antagonism reverses isoflurane ischemic neuroprotection</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>Isoflurane provides protection against severe forebrain ischemia in the rat. The authors hypothesized that this is attributable to interaction with the gamma-aminobutyric acid type A (GABAA) receptor resulting in altered time to onset of ischemic hippocampal depolarization.
Organotypic hippocampal slices were subjected to oxygen-glucose deprivation in the presence of isoflurane and combinations of GABAA (bicuculline) and GABAB (phaclofen) receptor antagonists. Cell death was measured. Rats were subjected to severe forebrain ischemia while anesthetized with fentanyl-nitrous oxide or 1.4% isoflurane. In the isoflurane group, rats also received intravenous bicuculline (0, 1, or 2 mg/kg). Neurologic and histologic outcomes and time to depolarization were assessed.
In slices, 2% isoflurane caused near-complete protection against oxygen-glucose deprivation. This was unaffected by coadministration of phaclofen but largely reversed by bicuculline. The GABAA agonist muscimol was also protective, having an effect equivalent to 1% isoflurane. In rats, isoflurane (0 mg bicuculline) improved neurologic and histologic outcome versus fentanyl-nitrous oxide (CA1 percentage of alive neurons: fentanyl-nitrous oxide, 15 +/- 7; isoflurane, 61 +/- 24). The isoflurane effect was reversed in a dose-dependent manner by bicuculline (CA1 percentage alive: 1 mg/kg, 44 +/- 22; 2 mg/kg, 21 +/- 15). Time to depolarization was delayed with isoflurane versus fentanyl-nitrous oxide (137 vs. 80 s) but was not affected by bicuculline (149 s). In contrast, postischemic time to repolarization was more rapid with fentanyl-nitrous oxide or isoflurane plus bicuculline versus isoflurane alone.
These studies are consistent with the hypothesis that the GABAA receptor serves as a major site of action for isoflurane neuroprotection both in vitro and in vivo. However, the mechanism by which this interaction confers in vivo protection cannot be attributed to effects on the duration of ischemic depolarization.</description><subject>Anesthesia</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain Ischemia - physiopathology</subject><subject>Brain Ischemia - prevention & control</subject><subject>GABA Antagonists - pharmacology</subject><subject>GABA-A Receptor Antagonists</subject><subject>In Vitro Techniques</subject><subject>Isoflurane - antagonists & inhibitors</subject><subject>Isoflurane - therapeutic use</subject><subject>Medical sciences</subject><subject>Neuroprotective Agents - antagonists & inhibitors</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, GABA-A - physiology</subject><issn>0003-3022</issn><issn>1528-1175</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtOwzAQhi0EoqVwBZQN7AJ-xI69RBUvqRILYB05zhiCkjjYSaWei3twJlwa6EjWeEb_PzP6EEoIviJY5dd4GzyjKcVY4DwWaXxEHKA54VSmhOT8EM1jj6UMUzpDJyF8xDLnTB6jGRESK6XkHNlnaMAM9RqS769Ut3XnynHY-Nok2tRVMmx6SHTiwUA_OJ_obtBvrqtDG3tr8AFCUgdnm9HrDuLXvEMbzR2M3vXeDdvhrjtFR1Y3Ac6mvECvd7cvy4d09XT_uLxZpYZhKVKjiaowtzijopQMSlJRoggRvFKZqjhgYxlnBoOtqCyFLnNrOMXaCiqznLEFutzNjas_RwhD0caToGnicW4MhZBcccFVFMqd0HgXggdb9L5utd8UBBdbxsUf4-KfcfHLOFrPpx1j2UK1N05Qo-BiEuhgdGMjGVOHvS5XROVSsh8T4IbH</recordid><startdate>200607</startdate><enddate>200607</enddate><creator>ELSERSY, Hazem</creator><creator>MIXCO, Javier</creator><creator>HUAXIN SHENG</creator><creator>PEARLSTEIN, Robert D</creator><creator>WARNER, David S</creator><general>Lippincott</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>200607</creationdate><title>Selective γ-aminobutyric acid type a receptor antagonism reverses isoflurane ischemic neuroprotection</title><author>ELSERSY, Hazem ; MIXCO, Javier ; HUAXIN SHENG ; PEARLSTEIN, Robert D ; WARNER, David S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3086-ca19d05f0426b83eb1d2191165d949d5e0cf353c0efd28b6ab7fc520af6284733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Anesthesia</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain Ischemia - physiopathology</topic><topic>Brain Ischemia - prevention & control</topic><topic>GABA Antagonists - pharmacology</topic><topic>GABA-A Receptor Antagonists</topic><topic>In Vitro Techniques</topic><topic>Isoflurane - antagonists & inhibitors</topic><topic>Isoflurane - therapeutic use</topic><topic>Medical sciences</topic><topic>Neuroprotective Agents - antagonists & inhibitors</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, GABA-A - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ELSERSY, Hazem</creatorcontrib><creatorcontrib>MIXCO, Javier</creatorcontrib><creatorcontrib>HUAXIN SHENG</creatorcontrib><creatorcontrib>PEARLSTEIN, Robert D</creatorcontrib><creatorcontrib>WARNER, David S</creatorcontrib><collection>Pascal-Francis</collection><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><jtitle>Anesthesiology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ELSERSY, Hazem</au><au>MIXCO, Javier</au><au>HUAXIN SHENG</au><au>PEARLSTEIN, Robert D</au><au>WARNER, David S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective γ-aminobutyric acid type a receptor antagonism reverses isoflurane ischemic neuroprotection</atitle><jtitle>Anesthesiology (Philadelphia)</jtitle><addtitle>Anesthesiology</addtitle><date>2006-07</date><risdate>2006</risdate><volume>105</volume><issue>1</issue><spage>81</spage><epage>90</epage><pages>81-90</pages><issn>0003-3022</issn><eissn>1528-1175</eissn><coden>ANESAV</coden><abstract>Isoflurane provides protection against severe forebrain ischemia in the rat. The authors hypothesized that this is attributable to interaction with the gamma-aminobutyric acid type A (GABAA) receptor resulting in altered time to onset of ischemic hippocampal depolarization.
Organotypic hippocampal slices were subjected to oxygen-glucose deprivation in the presence of isoflurane and combinations of GABAA (bicuculline) and GABAB (phaclofen) receptor antagonists. Cell death was measured. Rats were subjected to severe forebrain ischemia while anesthetized with fentanyl-nitrous oxide or 1.4% isoflurane. In the isoflurane group, rats also received intravenous bicuculline (0, 1, or 2 mg/kg). Neurologic and histologic outcomes and time to depolarization were assessed.
In slices, 2% isoflurane caused near-complete protection against oxygen-glucose deprivation. This was unaffected by coadministration of phaclofen but largely reversed by bicuculline. The GABAA agonist muscimol was also protective, having an effect equivalent to 1% isoflurane. In rats, isoflurane (0 mg bicuculline) improved neurologic and histologic outcome versus fentanyl-nitrous oxide (CA1 percentage of alive neurons: fentanyl-nitrous oxide, 15 +/- 7; isoflurane, 61 +/- 24). The isoflurane effect was reversed in a dose-dependent manner by bicuculline (CA1 percentage alive: 1 mg/kg, 44 +/- 22; 2 mg/kg, 21 +/- 15). Time to depolarization was delayed with isoflurane versus fentanyl-nitrous oxide (137 vs. 80 s) but was not affected by bicuculline (149 s). In contrast, postischemic time to repolarization was more rapid with fentanyl-nitrous oxide or isoflurane plus bicuculline versus isoflurane alone.
These studies are consistent with the hypothesis that the GABAA receptor serves as a major site of action for isoflurane neuroprotection both in vitro and in vivo. However, the mechanism by which this interaction confers in vivo protection cannot be attributed to effects on the duration of ischemic depolarization.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>16809998</pmid><doi>10.1097/00000542-200607000-00016</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anesthesia Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Brain Ischemia - physiopathology Brain Ischemia - prevention & control GABA Antagonists - pharmacology GABA-A Receptor Antagonists In Vitro Techniques Isoflurane - antagonists & inhibitors Isoflurane - therapeutic use Medical sciences Neuroprotective Agents - antagonists & inhibitors Neuroprotective Agents - therapeutic use Rats Rats, Sprague-Dawley Receptors, GABA-A - physiology |
| title | Selective γ-aminobutyric acid type a receptor antagonism reverses isoflurane ischemic neuroprotection |
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