Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model
Dodecafluoropentane emulsion (DDFPe) nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time wi...
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| Veröffentlicht in: | Molecular neurobiology 2015-10, Vol.52 (2), p.979-984 |
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| creator | Culp, W. C. Brown, A. T. Lowery, J. D. Arthur, M. C. Roberson, P. K. Skinner, R. D. |
| description | Dodecafluoropentane emulsion (DDFPe) nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time window for tissue plasminogen activator (tPA). Longer treatment windows will allow more patients more complete stroke recovery. We test DDFPe to safely extend the time window for tPA thrombolysis to 9 h after stroke. With IACUC approval, randomized New Zealand white rabbits (3.4–4.7 kg,
n
= 30) received angiography and 4-mm blood clot in the internal carotid artery for flow-directed middle cerebral artery occlusion. Seven failed and were discarded. Groups were IV tPA (
n
= 11), DDFPe + tPA (
n
= 7), and no therapy controls (
n
= 5). DDFPe (0.3 ml/kg, 2 % emulsion) IV dosing began at 1 h and continued at 90 min intervals for 6 doses in one test group; the other received saline injections. Both got standard IV tPA (0.9 mg/kg) therapy starting 9 h post stroke. At 24 h, neurological assessment scores (NAS, 0–18) were determined. Following brain removal percent stroke volume (%SV) was measured. Outcomes were compared with Kruskal-Wallis analysis. For NAS, DDFPe + tPA was improved overall,
p
= 0.0015, and vs. tPA alone,
p
= 0.0052. For %SV, DDFPe + tPA was improved overall,
p
= 0.0003 and vs. tPA alone,
p
= 0.0018. NAS controls and tPA alone were not different but %SV was,
p
= 0.0078. With delayed reperfusion, DDFPe + tPA was more effective than tPA alone in preserving functioning brain after stroke. DDFPe significantly extends the time window for tPA therapy. |
| doi_str_mv | 10.1007/s12035-015-9243-x |
| format | Article |
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n
= 30) received angiography and 4-mm blood clot in the internal carotid artery for flow-directed middle cerebral artery occlusion. Seven failed and were discarded. Groups were IV tPA (
n
= 11), DDFPe + tPA (
n
= 7), and no therapy controls (
n
= 5). DDFPe (0.3 ml/kg, 2 % emulsion) IV dosing began at 1 h and continued at 90 min intervals for 6 doses in one test group; the other received saline injections. Both got standard IV tPA (0.9 mg/kg) therapy starting 9 h post stroke. At 24 h, neurological assessment scores (NAS, 0–18) were determined. Following brain removal percent stroke volume (%SV) was measured. Outcomes were compared with Kruskal-Wallis analysis. For NAS, DDFPe + tPA was improved overall,
p
= 0.0015, and vs. tPA alone,
p
= 0.0052. For %SV, DDFPe + tPA was improved overall,
p
= 0.0003 and vs. tPA alone,
p
= 0.0018. NAS controls and tPA alone were not different but %SV was,
p
= 0.0078. With delayed reperfusion, DDFPe + tPA was more effective than tPA alone in preserving functioning brain after stroke. DDFPe significantly extends the time window for tPA therapy.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-015-9243-x</identifier><identifier>PMID: 26055229</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Cerebral Hemorrhage - chemically induced ; Disease Models, Animal ; Drug Administration Schedule ; Drug Evaluation, Preclinical ; Emulsions ; Female ; Fibrinolytic Agents - administration & dosage ; Fibrinolytic Agents - therapeutic use ; Fibrinolytic Agents - toxicity ; Fluorocarbons - administration & dosage ; Fluorocarbons - therapeutic use ; Infarction, Anterior Cerebral Artery - drug therapy ; Infarction, Anterior Cerebral Artery - pathology ; Infarction, Middle Cerebral Artery - drug therapy ; Infarction, Middle Cerebral Artery - pathology ; Infusions, Intravenous ; Male ; Neurobiology ; Neurology ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - therapeutic use ; Neurosciences ; Pharmacology ; Rabbits ; Random Allocation ; Reperfusion Injury - prevention & control ; Single-Blind Method ; Stroke ; Thrombolytic Therapy - adverse effects ; Thrombolytic Therapy - methods ; Time Factors ; Tissue Plasminogen Activator - administration & dosage ; Tissue Plasminogen Activator - therapeutic use ; Tissue Plasminogen Activator - toxicity</subject><ispartof>Molecular neurobiology, 2015-10, Vol.52 (2), p.979-984</ispartof><rights>Springer Science+Business Media New York 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-3588ec19b22d0adcd67928083c5eb2415afd5365f8193ffd01fe999e66c9f5ae3</citedby><cites>FETCH-LOGICAL-c573t-3588ec19b22d0adcd67928083c5eb2415afd5365f8193ffd01fe999e66c9f5ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-015-9243-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-015-9243-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26055229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Culp, W. C.</creatorcontrib><creatorcontrib>Brown, A. T.</creatorcontrib><creatorcontrib>Lowery, J. D.</creatorcontrib><creatorcontrib>Arthur, M. C.</creatorcontrib><creatorcontrib>Roberson, P. K.</creatorcontrib><creatorcontrib>Skinner, R. D.</creatorcontrib><title>Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Dodecafluoropentane emulsion (DDFPe) nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time window for tissue plasminogen activator (tPA). Longer treatment windows will allow more patients more complete stroke recovery. We test DDFPe to safely extend the time window for tPA thrombolysis to 9 h after stroke. With IACUC approval, randomized New Zealand white rabbits (3.4–4.7 kg,
n
= 30) received angiography and 4-mm blood clot in the internal carotid artery for flow-directed middle cerebral artery occlusion. Seven failed and were discarded. Groups were IV tPA (
n
= 11), DDFPe + tPA (
n
= 7), and no therapy controls (
n
= 5). DDFPe (0.3 ml/kg, 2 % emulsion) IV dosing began at 1 h and continued at 90 min intervals for 6 doses in one test group; the other received saline injections. Both got standard IV tPA (0.9 mg/kg) therapy starting 9 h post stroke. At 24 h, neurological assessment scores (NAS, 0–18) were determined. Following brain removal percent stroke volume (%SV) was measured. Outcomes were compared with Kruskal-Wallis analysis. For NAS, DDFPe + tPA was improved overall,
p
= 0.0015, and vs. tPA alone,
p
= 0.0052. For %SV, DDFPe + tPA was improved overall,
p
= 0.0003 and vs. tPA alone,
p
= 0.0018. NAS controls and tPA alone were not different but %SV was,
p
= 0.0078. With delayed reperfusion, DDFPe + tPA was more effective than tPA alone in preserving functioning brain after stroke. DDFPe significantly extends the time window for tPA therapy.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cerebral Hemorrhage - chemically induced</subject><subject>Disease Models, Animal</subject><subject>Drug Administration Schedule</subject><subject>Drug Evaluation, Preclinical</subject><subject>Emulsions</subject><subject>Female</subject><subject>Fibrinolytic Agents - administration & dosage</subject><subject>Fibrinolytic Agents - therapeutic use</subject><subject>Fibrinolytic Agents - toxicity</subject><subject>Fluorocarbons - administration & dosage</subject><subject>Fluorocarbons - therapeutic use</subject><subject>Infarction, Anterior Cerebral Artery - drug therapy</subject><subject>Infarction, Anterior Cerebral Artery - pathology</subject><subject>Infarction, Middle Cerebral Artery - drug therapy</subject><subject>Infarction, Middle Cerebral Artery - pathology</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neurosciences</subject><subject>Pharmacology</subject><subject>Rabbits</subject><subject>Random Allocation</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Single-Blind Method</subject><subject>Stroke</subject><subject>Thrombolytic Therapy - adverse effects</subject><subject>Thrombolytic Therapy - methods</subject><subject>Time Factors</subject><subject>Tissue Plasminogen Activator - administration & dosage</subject><subject>Tissue Plasminogen Activator - therapeutic use</subject><subject>Tissue Plasminogen Activator - toxicity</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkctuFDEQRS1ERIbAB7BBlthk0-BHu21vkKIwPKREIBjE0nLb5aRDjz3Y3WHy93g0IQpISKxqUaduVd2L0DNKXlJC5KtCGeGiIVQ0mrW82T5ACyqEbihV7CFaEKV5I7tWHaLHpVwRwhgl8hE6ZB0RgjG9QKs3yYOzYZxTThuIk42Al-t5LEOKeLmdIPqCvw3Rp584pIynTyd4dQnZbm7wELHFn23fDxP-MuX0HfB5lRufoINgxwJPb-sR-vp2uTp935x9fPfh9OSscULyqeFCKXBU94x5Yr3zndRMEcWdgJ61VNjgBe9EUFTzEDyhAbTW0HVOB2GBH6HXe93N3K_Bu3p-tqPZ5GFt841JdjB_duJwaS7StWm1Vop3VeD4ViCnHzOUyayH4mAcqwtpLobK6phUWsr_QInmumOkreiLv9CrNOdYndhRSlaO7nbTPeVyKiVDuLubErOL1-zjNTVes4vXbOvM8_sP3038zrMCbA-U2ooXkO-t_qfqL_SfsLk</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Culp, W. C.</creator><creator>Brown, A. T.</creator><creator>Lowery, J. D.</creator><creator>Arthur, M. C.</creator><creator>Roberson, P. K.</creator><creator>Skinner, R. 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C. ; Brown, A. T. ; Lowery, J. D. ; Arthur, M. C. ; Roberson, P. K. ; Skinner, R. D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-3588ec19b22d0adcd67928083c5eb2415afd5365f8193ffd01fe999e66c9f5ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Cerebral Hemorrhage - chemically induced</topic><topic>Disease Models, Animal</topic><topic>Drug Administration Schedule</topic><topic>Drug Evaluation, Preclinical</topic><topic>Emulsions</topic><topic>Female</topic><topic>Fibrinolytic Agents - administration & dosage</topic><topic>Fibrinolytic Agents - therapeutic use</topic><topic>Fibrinolytic Agents - toxicity</topic><topic>Fluorocarbons - administration & dosage</topic><topic>Fluorocarbons - therapeutic use</topic><topic>Infarction, Anterior Cerebral Artery - drug therapy</topic><topic>Infarction, Anterior Cerebral Artery - pathology</topic><topic>Infarction, Middle Cerebral Artery - drug therapy</topic><topic>Infarction, Middle Cerebral Artery - pathology</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neuroprotective Agents - administration & dosage</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Neurosciences</topic><topic>Pharmacology</topic><topic>Rabbits</topic><topic>Random Allocation</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Single-Blind Method</topic><topic>Stroke</topic><topic>Thrombolytic Therapy - adverse effects</topic><topic>Thrombolytic Therapy - methods</topic><topic>Time Factors</topic><topic>Tissue Plasminogen Activator - administration & dosage</topic><topic>Tissue Plasminogen Activator - therapeutic use</topic><topic>Tissue Plasminogen Activator - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Culp, W. C.</creatorcontrib><creatorcontrib>Brown, A. T.</creatorcontrib><creatorcontrib>Lowery, J. D.</creatorcontrib><creatorcontrib>Arthur, M. C.</creatorcontrib><creatorcontrib>Roberson, P. K.</creatorcontrib><creatorcontrib>Skinner, R. 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C.</au><au>Brown, A. T.</au><au>Lowery, J. D.</au><au>Arthur, M. C.</au><au>Roberson, P. K.</au><au>Skinner, R. D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>52</volume><issue>2</issue><spage>979</spage><epage>984</epage><pages>979-984</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Dodecafluoropentane emulsion (DDFPe) nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time window for tissue plasminogen activator (tPA). Longer treatment windows will allow more patients more complete stroke recovery. We test DDFPe to safely extend the time window for tPA thrombolysis to 9 h after stroke. With IACUC approval, randomized New Zealand white rabbits (3.4–4.7 kg,
n
= 30) received angiography and 4-mm blood clot in the internal carotid artery for flow-directed middle cerebral artery occlusion. Seven failed and were discarded. Groups were IV tPA (
n
= 11), DDFPe + tPA (
n
= 7), and no therapy controls (
n
= 5). DDFPe (0.3 ml/kg, 2 % emulsion) IV dosing began at 1 h and continued at 90 min intervals for 6 doses in one test group; the other received saline injections. Both got standard IV tPA (0.9 mg/kg) therapy starting 9 h post stroke. At 24 h, neurological assessment scores (NAS, 0–18) were determined. Following brain removal percent stroke volume (%SV) was measured. Outcomes were compared with Kruskal-Wallis analysis. For NAS, DDFPe + tPA was improved overall,
p
= 0.0015, and vs. tPA alone,
p
= 0.0052. For %SV, DDFPe + tPA was improved overall,
p
= 0.0003 and vs. tPA alone,
p
= 0.0018. NAS controls and tPA alone were not different but %SV was,
p
= 0.0078. With delayed reperfusion, DDFPe + tPA was more effective than tPA alone in preserving functioning brain after stroke. DDFPe significantly extends the time window for tPA therapy.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26055229</pmid><doi>10.1007/s12035-015-9243-x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular neurobiology, 2015-10, Vol.52 (2), p.979-984 |
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| subjects | Animals Biomedical and Life Sciences Biomedicine Cell Biology Cerebral Hemorrhage - chemically induced Disease Models, Animal Drug Administration Schedule Drug Evaluation, Preclinical Emulsions Female Fibrinolytic Agents - administration & dosage Fibrinolytic Agents - therapeutic use Fibrinolytic Agents - toxicity Fluorocarbons - administration & dosage Fluorocarbons - therapeutic use Infarction, Anterior Cerebral Artery - drug therapy Infarction, Anterior Cerebral Artery - pathology Infarction, Middle Cerebral Artery - drug therapy Infarction, Middle Cerebral Artery - pathology Infusions, Intravenous Male Neurobiology Neurology Neuroprotective Agents - administration & dosage Neuroprotective Agents - therapeutic use Neurosciences Pharmacology Rabbits Random Allocation Reperfusion Injury - prevention & control Single-Blind Method Stroke Thrombolytic Therapy - adverse effects Thrombolytic Therapy - methods Time Factors Tissue Plasminogen Activator - administration & dosage Tissue Plasminogen Activator - therapeutic use Tissue Plasminogen Activator - toxicity |
| title | Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model |
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