Diazepam Promotes ATP Recovery and Prevents Cytochrome c Release in Hippocampal Slices After In Vitro Ischemia
: Benzodiazepines protect hippocampal neurons when administered within the first few hours after transient cerebral ischemia. Here, we examined the ability of diazepam to prevent early signals of cell injury (before cell death) after in vitro ischemia. Ischemia in vitro or in vivo causes a rapid dep...
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creator | Galeffi, Francesca Sinnar, Shamim Schwartz‐Bloom, Rochelle D. |
description | : Benzodiazepines protect hippocampal neurons when
administered within the first few hours after transient cerebral ischemia.
Here, we examined the ability of diazepam to prevent early signals of cell
injury (before cell death) after in vitro ischemia. Ischemia in vitro or in
vivo causes a rapid depletion of ATP and the generation of cell death signals,
such as the release of cytochrome c from mitochondria. Hippocampal
slices from adult rats were subjected to 7 min of oxygen‐glucose deprivation
(OGD) and assessed histologically 3 h after reoxygenation. At this time, area
CA1 neurons appeared viable, although slight abnormalities in structure were
evident. Immediately following OGD, ATP levels in hippocampus were decreased
by 70%, and they recovered partially over the next 3 h of reoxygenation. When
diazepam was included in the reoxygenation buffer, ATP levels recovered
completely by 3 h after OGD. The effects of diazepam were blocked by
picrotoxin, indicating that the protection was mediated by an influx of
Cl‐ through the GABAA receptor. It is interesting that
the benzodiazepine antagonist flumazenil did not prevent the action of
diazepam, as has been shown in other studies using the hippocampus. Two hours
after OGD, the partial recovery of ATP levels occurred simultaneously with an
increase of cytochrome c (∼400%) in the cytosol. When diazepam
was included in the reoxygenation buffer, it completely prevented the increase
in cytosolic cytochrome c. Thus, complete recovery of ATP and
prevention of cytochrome c release from mitochondria can be achieved when diazepam is given after the loss of ATP induced by OGD. |
doi_str_mv | 10.1046/j.1471-4159.2000.0751242.x |
format | Article |
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administered within the first few hours after transient cerebral ischemia.
Here, we examined the ability of diazepam to prevent early signals of cell
injury (before cell death) after in vitro ischemia. Ischemia in vitro or in
vivo causes a rapid depletion of ATP and the generation of cell death signals,
such as the release of cytochrome c from mitochondria. Hippocampal
slices from adult rats were subjected to 7 min of oxygen‐glucose deprivation
(OGD) and assessed histologically 3 h after reoxygenation. At this time, area
CA1 neurons appeared viable, although slight abnormalities in structure were
evident. Immediately following OGD, ATP levels in hippocampus were decreased
by 70%, and they recovered partially over the next 3 h of reoxygenation. When
diazepam was included in the reoxygenation buffer, ATP levels recovered
completely by 3 h after OGD. The effects of diazepam were blocked by
picrotoxin, indicating that the protection was mediated by an influx of
Cl‐ through the GABAA receptor. It is interesting that
the benzodiazepine antagonist flumazenil did not prevent the action of
diazepam, as has been shown in other studies using the hippocampus. Two hours
after OGD, the partial recovery of ATP levels occurred simultaneously with an
increase of cytochrome c (∼400%) in the cytosol. When diazepam
was included in the reoxygenation buffer, it completely prevented the increase
in cytosolic cytochrome c. Thus, complete recovery of ATP and
prevention of cytochrome c release from mitochondria can be achieved when diazepam is given after the loss of ATP induced by OGD.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.2000.0751242.x</identifier><identifier>PMID: 10936207</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford UK: Blackwell Science Ltd</publisher><subject>Adenosine Triphosphate - metabolism ; Animals ; ATP ; Biological and medical sciences ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Cytochrome c ; Cytochrome c Group - antagonists & inhibitors ; Cytochrome c Group - metabolism ; Cytosol - metabolism ; Diazepam ; Diazepam - pharmacology ; GABAA receptor ; Glucose - metabolism ; Glucose - pharmacology ; Hippocampal slice ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hippocampus - pathology ; Hypoxia, Brain - metabolism ; Immunohistochemistry ; In vitro ischemia ; In Vitro Techniques ; Male ; Medical sciences ; Microtubule-Associated Proteins - metabolism ; Mitochondria - metabolism ; Neurology ; Rats ; Rats, Sprague-Dawley ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Journal of neurochemistry, 2000-09, Vol.75 (3), p.1242-1249</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4992-c5b2e1bc8b5874b310a2932a83660524dc43ab4b2e981d6e8d53836fc005c3643</citedby><cites>FETCH-LOGICAL-c4992-c5b2e1bc8b5874b310a2932a83660524dc43ab4b2e981d6e8d53836fc005c3643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.2000.0751242.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.2000.0751242.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=801659$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10936207$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Galeffi, Francesca</creatorcontrib><creatorcontrib>Sinnar, Shamim</creatorcontrib><creatorcontrib>Schwartz‐Bloom, Rochelle D.</creatorcontrib><title>Diazepam Promotes ATP Recovery and Prevents Cytochrome c Release in Hippocampal Slices After In Vitro Ischemia</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>: Benzodiazepines protect hippocampal neurons when
administered within the first few hours after transient cerebral ischemia.
Here, we examined the ability of diazepam to prevent early signals of cell
injury (before cell death) after in vitro ischemia. Ischemia in vitro or in
vivo causes a rapid depletion of ATP and the generation of cell death signals,
such as the release of cytochrome c from mitochondria. Hippocampal
slices from adult rats were subjected to 7 min of oxygen‐glucose deprivation
(OGD) and assessed histologically 3 h after reoxygenation. At this time, area
CA1 neurons appeared viable, although slight abnormalities in structure were
evident. Immediately following OGD, ATP levels in hippocampus were decreased
by 70%, and they recovered partially over the next 3 h of reoxygenation. When
diazepam was included in the reoxygenation buffer, ATP levels recovered
completely by 3 h after OGD. The effects of diazepam were blocked by
picrotoxin, indicating that the protection was mediated by an influx of
Cl‐ through the GABAA receptor. It is interesting that
the benzodiazepine antagonist flumazenil did not prevent the action of
diazepam, as has been shown in other studies using the hippocampus. Two hours
after OGD, the partial recovery of ATP levels occurred simultaneously with an
increase of cytochrome c (∼400%) in the cytosol. When diazepam
was included in the reoxygenation buffer, it completely prevented the increase
in cytosolic cytochrome c. Thus, complete recovery of ATP and
prevention of cytochrome c release from mitochondria can be achieved when diazepam is given after the loss of ATP induced by OGD.</description><subject>Adenosine Triphosphate - metabolism</subject><subject>Animals</subject><subject>ATP</subject><subject>Biological and medical sciences</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Cytochrome c</subject><subject>Cytochrome c Group - antagonists & inhibitors</subject><subject>Cytochrome c Group - metabolism</subject><subject>Cytosol - metabolism</subject><subject>Diazepam</subject><subject>Diazepam - pharmacology</subject><subject>GABAA receptor</subject><subject>Glucose - metabolism</subject><subject>Glucose - pharmacology</subject><subject>Hippocampal slice</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Hypoxia, Brain - metabolism</subject><subject>Immunohistochemistry</subject><subject>In vitro ischemia</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Mitochondria - metabolism</subject><subject>Neurology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkUtv1DAURi0EotPCX0AWSN0lvX7kxa5MaTuoggoKW8txblSPkjjYmdLh1-NoooodYmVZ37kP3UPIWwYpA5mfbVMmC5ZIllUpB4AUioxxydPHZ2T1FD0nKwDOEwGSH5HjELYALJc5e0mOGFQi51CsyHBh9W8cdU9vvevdhIGe393Sr2jcA_o91UMTE3zAYQp0vZ-cuY8cUhORDnVAagd6bcfRGd2PuqPfOmvmJu2Enm4G-sNO3tFNMPfYW_2KvGh1F_D18p6Q75cf79bXyc2Xq836_CYxsqp4YrKaI6tNWWdlIWvBQPNKcF2KPIeMy8ZIoWsZoapkTY5lk4mYtQYgMyKX4oScHvqO3v3cYZhUb4PBrtMDul1QBSsEL-W_QVbkhYhDIvj-ABrvQvDYqtHbXvu9YqBmLWqr5tur-fZq1qIWLeoxFr9ZpuzqHpu_Sg8eIvBuAXQwumu9HowNT1wZzWVVpD4cqF-2w_1_LKA-fV4vH_EHaMuoBQ</recordid><startdate>200009</startdate><enddate>200009</enddate><creator>Galeffi, Francesca</creator><creator>Sinnar, Shamim</creator><creator>Schwartz‐Bloom, Rochelle D.</creator><general>Blackwell Science Ltd</general><general>Blackwell</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>200009</creationdate><title>Diazepam Promotes ATP Recovery and Prevents Cytochrome c Release in Hippocampal Slices After In Vitro Ischemia</title><author>Galeffi, Francesca ; Sinnar, Shamim ; Schwartz‐Bloom, Rochelle D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4992-c5b2e1bc8b5874b310a2932a83660524dc43ab4b2e981d6e8d53836fc005c3643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adenosine Triphosphate - metabolism</topic><topic>Animals</topic><topic>ATP</topic><topic>Biological and medical sciences</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - pathology</topic><topic>Cytochrome c</topic><topic>Cytochrome c Group - antagonists & inhibitors</topic><topic>Cytochrome c Group - metabolism</topic><topic>Cytosol - metabolism</topic><topic>Diazepam</topic><topic>Diazepam - pharmacology</topic><topic>GABAA receptor</topic><topic>Glucose - metabolism</topic><topic>Glucose - pharmacology</topic><topic>Hippocampal slice</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Hypoxia, Brain - metabolism</topic><topic>Immunohistochemistry</topic><topic>In vitro ischemia</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Mitochondria - metabolism</topic><topic>Neurology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Galeffi, Francesca</creatorcontrib><creatorcontrib>Sinnar, Shamim</creatorcontrib><creatorcontrib>Schwartz‐Bloom, Rochelle D.</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Galeffi, Francesca</au><au>Sinnar, Shamim</au><au>Schwartz‐Bloom, Rochelle D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diazepam Promotes ATP Recovery and Prevents Cytochrome c Release in Hippocampal Slices After In Vitro Ischemia</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2000-09</date><risdate>2000</risdate><volume>75</volume><issue>3</issue><spage>1242</spage><epage>1249</epage><pages>1242-1249</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>: Benzodiazepines protect hippocampal neurons when
administered within the first few hours after transient cerebral ischemia.
Here, we examined the ability of diazepam to prevent early signals of cell
injury (before cell death) after in vitro ischemia. Ischemia in vitro or in
vivo causes a rapid depletion of ATP and the generation of cell death signals,
such as the release of cytochrome c from mitochondria. Hippocampal
slices from adult rats were subjected to 7 min of oxygen‐glucose deprivation
(OGD) and assessed histologically 3 h after reoxygenation. At this time, area
CA1 neurons appeared viable, although slight abnormalities in structure were
evident. Immediately following OGD, ATP levels in hippocampus were decreased
by 70%, and they recovered partially over the next 3 h of reoxygenation. When
diazepam was included in the reoxygenation buffer, ATP levels recovered
completely by 3 h after OGD. The effects of diazepam were blocked by
picrotoxin, indicating that the protection was mediated by an influx of
Cl‐ through the GABAA receptor. It is interesting that
the benzodiazepine antagonist flumazenil did not prevent the action of
diazepam, as has been shown in other studies using the hippocampus. Two hours
after OGD, the partial recovery of ATP levels occurred simultaneously with an
increase of cytochrome c (∼400%) in the cytosol. When diazepam
was included in the reoxygenation buffer, it completely prevented the increase
in cytosolic cytochrome c. Thus, complete recovery of ATP and
prevention of cytochrome c release from mitochondria can be achieved when diazepam is given after the loss of ATP induced by OGD.</abstract><cop>Oxford UK</cop><pub>Blackwell Science Ltd</pub><pmid>10936207</pmid><doi>10.1046/j.1471-4159.2000.0751242.x</doi><tpages>8</tpages></addata></record> |
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subjects | Adenosine Triphosphate - metabolism Animals ATP Biological and medical sciences Brain Ischemia - metabolism Brain Ischemia - pathology Cytochrome c Cytochrome c Group - antagonists & inhibitors Cytochrome c Group - metabolism Cytosol - metabolism Diazepam Diazepam - pharmacology GABAA receptor Glucose - metabolism Glucose - pharmacology Hippocampal slice Hippocampus - drug effects Hippocampus - metabolism Hippocampus - pathology Hypoxia, Brain - metabolism Immunohistochemistry In vitro ischemia In Vitro Techniques Male Medical sciences Microtubule-Associated Proteins - metabolism Mitochondria - metabolism Neurology Rats Rats, Sprague-Dawley Vascular diseases and vascular malformations of the nervous system |
title | Diazepam Promotes ATP Recovery and Prevents Cytochrome c Release in Hippocampal Slices After In Vitro Ischemia |
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