Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188)
Vepoloxamer is an amphipathic polymer that has shown potent hemorrheologic, cytoprotective, and anti-inflammatory effects in both pre-clinical and clinical studies. This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and cognitive functional recovery in rats...
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| Veröffentlicht in: | Journal of neurotrauma 2018-02, Vol.35 (4), p.661-670 |
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| container_title | Journal of neurotrauma |
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| creator | Zhang, Yanlu Chopp, Michael Emanuele, Martin Zhang, Li Zhang, Zheng Gang Lu, Mei Zhang, Talan Mahmood, Asim Xiong, Ye |
| description | Vepoloxamer is an amphipathic polymer that has shown potent hemorrheologic, cytoprotective, and anti-inflammatory effects in both pre-clinical and clinical studies. This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and cognitive functional recovery in rats after traumatic brain injury (TBI) induced by controlled cortical impact. Young adult male Wistar rats were randomly divided into the following groups: 1) sham; 2) saline; or 3) vepoloxamer. Vepoloxamer (300 mg/kg) or saline was administered over 60 min via intravenous infusion into tail veins starting at 2 h post-injury. Sensorimotor function and spatial learning were assessed using a modified neurological severity score and foot fault test, and Morris water maze test, respectively. The animals were sacrificed 35 days after injury and their brains were processed for measurement of lesion volume and neuroinflammation. Compared with the saline treatment, vepoloxamer initiated 2 h post-injury significantly improved sensorimotor functional recovery (Days 1-35; p |
| doi_str_mv | 10.1089/neu.2017.5284 |
| format | Article |
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This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and cognitive functional recovery in rats after traumatic brain injury (TBI) induced by controlled cortical impact. Young adult male Wistar rats were randomly divided into the following groups: 1) sham; 2) saline; or 3) vepoloxamer. Vepoloxamer (300 mg/kg) or saline was administered over 60 min via intravenous infusion into tail veins starting at 2 h post-injury. Sensorimotor function and spatial learning were assessed using a modified neurological severity score and foot fault test, and Morris water maze test, respectively. The animals were sacrificed 35 days after injury and their brains were processed for measurement of lesion volume and neuroinflammation. Compared with the saline treatment, vepoloxamer initiated 2 h post-injury significantly improved sensorimotor functional recovery (Days 1-35; p < 0.0001) and spatial learning (Days 32-35; p < 0.0001), reduced cortical lesion volume by 20%, and reduced activation of microglia/macrophages and astrogliosis in many brain regions including injured cortex, corpus callosum, and hippocampus, as well as normalized the bleeding time and reduced brain hemorrhage and microthrombosis formation. In summary, vepoloxamer treatment initiated 2 h post-injury provides neuroprotection and anti-inflammation in rats after TBI and improves functional outcome, indicating that vepoloxamer treatment may have potential value for treatment of TBI. Further investigation of the optimal dose and therapeutic window of vepoloxamer treatment for TBI and the mechanisms underlying beneficial effects are warranted.</description><identifier>ISSN: 0897-7151</identifier><identifier>EISSN: 1557-9042</identifier><identifier>DOI: 10.1089/neu.2017.5284</identifier><identifier>PMID: 29121826</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animal cognition ; Animals ; Apoptosis ; Brain Injuries, Traumatic - pathology ; Brain research ; Cell activation ; Cognitive ability ; Corpus callosum ; Cortex ; Epidemiology ; Gliosis ; Head injuries ; Hemorrhage ; Inflammation ; Intravenous administration ; Macrophages ; Male ; Microglia ; Neurology ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Neurosurgery ; Poloxamer - pharmacology ; Polyethylene ; Rats ; Rats, Wistar ; Recovery of function ; Recovery of Function - drug effects ; Rodents ; Sensorimotor system ; Spatial discrimination learning ; Traumatic brain injury</subject><ispartof>Journal of neurotrauma, 2018-02, Vol.35 (4), p.661-670</ispartof><rights>(©) Copyright 2018, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c321t-525a6ceead56bc27b6f6ae7a1545b72e9bd091845e7f1dcfb17746a9293d7f63</citedby><cites>FETCH-LOGICAL-c321t-525a6ceead56bc27b6f6ae7a1545b72e9bd091845e7f1dcfb17746a9293d7f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29121826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yanlu</creatorcontrib><creatorcontrib>Chopp, Michael</creatorcontrib><creatorcontrib>Emanuele, Martin</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Zhang, Zheng Gang</creatorcontrib><creatorcontrib>Lu, Mei</creatorcontrib><creatorcontrib>Zhang, Talan</creatorcontrib><creatorcontrib>Mahmood, Asim</creatorcontrib><creatorcontrib>Xiong, Ye</creatorcontrib><title>Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188)</title><title>Journal of neurotrauma</title><addtitle>J Neurotrauma</addtitle><description>Vepoloxamer is an amphipathic polymer that has shown potent hemorrheologic, cytoprotective, and anti-inflammatory effects in both pre-clinical and clinical studies. This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and cognitive functional recovery in rats after traumatic brain injury (TBI) induced by controlled cortical impact. Young adult male Wistar rats were randomly divided into the following groups: 1) sham; 2) saline; or 3) vepoloxamer. Vepoloxamer (300 mg/kg) or saline was administered over 60 min via intravenous infusion into tail veins starting at 2 h post-injury. Sensorimotor function and spatial learning were assessed using a modified neurological severity score and foot fault test, and Morris water maze test, respectively. The animals were sacrificed 35 days after injury and their brains were processed for measurement of lesion volume and neuroinflammation. Compared with the saline treatment, vepoloxamer initiated 2 h post-injury significantly improved sensorimotor functional recovery (Days 1-35; p < 0.0001) and spatial learning (Days 32-35; p < 0.0001), reduced cortical lesion volume by 20%, and reduced activation of microglia/macrophages and astrogliosis in many brain regions including injured cortex, corpus callosum, and hippocampus, as well as normalized the bleeding time and reduced brain hemorrhage and microthrombosis formation. In summary, vepoloxamer treatment initiated 2 h post-injury provides neuroprotection and anti-inflammation in rats after TBI and improves functional outcome, indicating that vepoloxamer treatment may have potential value for treatment of TBI. Further investigation of the optimal dose and therapeutic window of vepoloxamer treatment for TBI and the mechanisms underlying beneficial effects are warranted.</description><subject>Animal cognition</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Brain Injuries, Traumatic - pathology</subject><subject>Brain research</subject><subject>Cell activation</subject><subject>Cognitive ability</subject><subject>Corpus callosum</subject><subject>Cortex</subject><subject>Epidemiology</subject><subject>Gliosis</subject><subject>Head injuries</subject><subject>Hemorrhage</subject><subject>Inflammation</subject><subject>Intravenous administration</subject><subject>Macrophages</subject><subject>Male</subject><subject>Microglia</subject><subject>Neurology</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neurosurgery</subject><subject>Poloxamer - pharmacology</subject><subject>Polyethylene</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Recovery of function</subject><subject>Recovery of Function - drug effects</subject><subject>Rodents</subject><subject>Sensorimotor system</subject><subject>Spatial discrimination learning</subject><subject>Traumatic brain injury</subject><issn>0897-7151</issn><issn>1557-9042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</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>eNpd0M9LwzAUwPEgipvTo1cJeJmHzry0SZqjDn8MJu5QvIa0fcWO_phJi-6_t2NzB0-Blw-Px5eQa2AzYLG-b7CfcQZqJngcnZAxCKECzSJ-SsbDvwoUCBiRC-_XjEEouTonI66BQ8zlmLwlDm1XY9PRtqCJs31tuzKjj86WDV00695t6XfZfdIP3LRV-2NrdHS66l1ZlJjT1XEGcXx3Sc4KW3m8OrwTkjw_JfPXYPn-spg_LIMs5NAFggsrM0SbC5lmXKWykBaVBRGJVHHUac40xJFAVUCeFSkoFUmruQ5zVchwQqb7tRvXfvXoO1OXPsOqsg22vTegZcgVV0oN9PYfXbe9a4bjBqV1CEJzPqhgrzLXeu-wMBtX1tZtDTCzy2yGzGaX2ewyD_7msLVPa8yP-q9r-AuocXdN</recordid><startdate>20180215</startdate><enddate>20180215</enddate><creator>Zhang, Yanlu</creator><creator>Chopp, Michael</creator><creator>Emanuele, Martin</creator><creator>Zhang, Li</creator><creator>Zhang, Zheng Gang</creator><creator>Lu, Mei</creator><creator>Zhang, Talan</creator><creator>Mahmood, Asim</creator><creator>Xiong, Ye</creator><general>Mary Ann Liebert, 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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</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>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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20180215</creationdate><title>Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188)</title><author>Zhang, Yanlu ; Chopp, Michael ; Emanuele, Martin ; Zhang, Li ; Zhang, Zheng Gang ; Lu, Mei ; Zhang, Talan ; Mahmood, Asim ; Xiong, Ye</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321t-525a6ceead56bc27b6f6ae7a1545b72e9bd091845e7f1dcfb17746a9293d7f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animal cognition</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Brain Injuries, Traumatic - pathology</topic><topic>Brain research</topic><topic>Cell activation</topic><topic>Cognitive ability</topic><topic>Corpus callosum</topic><topic>Cortex</topic><topic>Epidemiology</topic><topic>Gliosis</topic><topic>Head injuries</topic><topic>Hemorrhage</topic><topic>Inflammation</topic><topic>Intravenous administration</topic><topic>Macrophages</topic><topic>Male</topic><topic>Microglia</topic><topic>Neurology</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neurosurgery</topic><topic>Poloxamer - pharmacology</topic><topic>Polyethylene</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Recovery of function</topic><topic>Recovery of Function - drug effects</topic><topic>Rodents</topic><topic>Sensorimotor system</topic><topic>Spatial discrimination learning</topic><topic>Traumatic brain injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yanlu</creatorcontrib><creatorcontrib>Chopp, Michael</creatorcontrib><creatorcontrib>Emanuele, Martin</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Zhang, Zheng Gang</creatorcontrib><creatorcontrib>Lu, Mei</creatorcontrib><creatorcontrib>Zhang, Talan</creatorcontrib><creatorcontrib>Mahmood, Asim</creatorcontrib><creatorcontrib>Xiong, Ye</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>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><jtitle>Journal of neurotrauma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yanlu</au><au>Chopp, Michael</au><au>Emanuele, Martin</au><au>Zhang, Li</au><au>Zhang, Zheng Gang</au><au>Lu, Mei</au><au>Zhang, Talan</au><au>Mahmood, Asim</au><au>Xiong, Ye</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188)</atitle><jtitle>Journal of neurotrauma</jtitle><addtitle>J Neurotrauma</addtitle><date>2018-02-15</date><risdate>2018</risdate><volume>35</volume><issue>4</issue><spage>661</spage><epage>670</epage><pages>661-670</pages><issn>0897-7151</issn><eissn>1557-9042</eissn><abstract>Vepoloxamer is an amphipathic polymer that has shown potent hemorrheologic, cytoprotective, and anti-inflammatory effects in both pre-clinical and clinical studies. This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and cognitive functional recovery in rats after traumatic brain injury (TBI) induced by controlled cortical impact. Young adult male Wistar rats were randomly divided into the following groups: 1) sham; 2) saline; or 3) vepoloxamer. Vepoloxamer (300 mg/kg) or saline was administered over 60 min via intravenous infusion into tail veins starting at 2 h post-injury. Sensorimotor function and spatial learning were assessed using a modified neurological severity score and foot fault test, and Morris water maze test, respectively. The animals were sacrificed 35 days after injury and their brains were processed for measurement of lesion volume and neuroinflammation. Compared with the saline treatment, vepoloxamer initiated 2 h post-injury significantly improved sensorimotor functional recovery (Days 1-35; p < 0.0001) and spatial learning (Days 32-35; p < 0.0001), reduced cortical lesion volume by 20%, and reduced activation of microglia/macrophages and astrogliosis in many brain regions including injured cortex, corpus callosum, and hippocampus, as well as normalized the bleeding time and reduced brain hemorrhage and microthrombosis formation. In summary, vepoloxamer treatment initiated 2 h post-injury provides neuroprotection and anti-inflammation in rats after TBI and improves functional outcome, indicating that vepoloxamer treatment may have potential value for treatment of TBI. Further investigation of the optimal dose and therapeutic window of vepoloxamer treatment for TBI and the mechanisms underlying beneficial effects are warranted.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>29121826</pmid><doi>10.1089/neu.2017.5284</doi><tpages>10</tpages></addata></record> |
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| language | eng |
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| subjects | Animal cognition Animals Apoptosis Brain Injuries, Traumatic - pathology Brain research Cell activation Cognitive ability Corpus callosum Cortex Epidemiology Gliosis Head injuries Hemorrhage Inflammation Intravenous administration Macrophages Male Microglia Neurology Neuroprotection Neuroprotective Agents - pharmacology Neurosurgery Poloxamer - pharmacology Polyethylene Rats Rats, Wistar Recovery of function Recovery of Function - drug effects Rodents Sensorimotor system Spatial discrimination learning Traumatic brain injury |
| title | Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188) |
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